Adenomatous Polyposis Coli: A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Genes, APC: Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.Intestinal Polyps: Discrete abnormal tissue masses that protrude into the lumen of the INTESTINE. A polyp is attached to the intestinal wall either by a stalk, pedunculus, or by a broad base.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Axin Protein: A scaffolding protein that is a critical component of the axin signaling complex which binds to ADENOMATOUS POLYPOSIS COLI PROTEIN; GLYCOGEN SYNTHASE KINASE 3; and CASEIN KINASE I.Adenomatous Polyps: Benign neoplasms derived from glandular epithelium. (From Stedman, 25th ed)Intestinal Polyposis: The growth of INTESTINAL POLYPS. Growth processes include neoplastic (ADENOMA and CARCINOMA) and non-neoplastic (hyperplastic, mucosal, inflammatory, and other polyps).Fibromatosis, Aggressive: A childhood counterpart of abdominal or extra-abdominal desmoid tumors, characterized by firm subcutaneous nodules that grow rapidly in any part of the body but do not metastasize. The adult form of abdominal fibromatosis is FIBROMATOSIS, ABDOMINAL. (Stedman, 25th ed)Adenoma: A benign epithelial tumor with a glandular organization.Intestinal Neoplasms: Tumors or cancer of the INTESTINES.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Gardner Syndrome: A variant of ADENOMATOUS POLYPOSIS COLI caused by mutation in the APC gene (GENES, APC) on CHROMOSOME 5. It is characterized by not only the presence of multiple colonic polyposis but also extracolonic ADENOMATOUS POLYPS in the UPPER GASTROINTESTINAL TRACT; the EYE; the SKIN; the SKULL; and the FACIAL BONES; as well as malignancy in organs other than the GI tract.Colonic Neoplasms: Tumors or cancer of the COLON.Polyps: Discrete abnormal tissue masses that protrude into the lumen of the DIGESTIVE TRACT or the RESPIRATORY TRACT. Polyps can be spheroidal, hemispheroidal, or irregular mound-shaped structures attached to the MUCOUS MEMBRANE of the lumen wall either by a stalk, pedunculus, or by a broad base.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Fibromatosis, Abdominal: A relatively large mass of unusually firm scarlike connective tissue resulting from active participation of fibroblasts, occurring most frequently in the abdominal muscles of women who have borne children. The fibroblasts infiltrate surrounding muscle and fascia. (Stedman, 25th ed)Chromosomes, Human, Pair 5: One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Duodenal Neoplasms: Tumors or cancer of the DUODENUM.Colonic Polyps: Discrete tissue masses that protrude into the lumen of the COLON. These POLYPS are connected to the wall of the colon either by a stalk, pedunculus, or by a broad base.TCF Transcription Factors: A family of DNA-binding proteins that are primarily expressed in T-LYMPHOCYTES. They interact with BETA CATENIN and serve as transcriptional activators and repressors in a variety of developmental processes.Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.Proctocolectomy, Restorative: A surgical procedure involving the excision of the COLON and RECTUM and the formation of an ILEOANAL RESERVOIR (pouch). In patients with intestinal diseases, such as ulcerative colitis, this procedure avoids the need for an OSTOMY by allowing for transanal defecation.Armadillo Domain Proteins: A family of proteins that contain several 42-amino acid repeat domains and are homologous to the Drosophila armadillo protein. They bind to other proteins through their armadillo domains and play a variety of roles in the CELL including SIGNAL TRANSDUCTION, regulation of DESMOSOME assembly, and CELL ADHESION.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Transcription Factor 7-Like 2 Protein: A transcription factor that takes part in WNT signaling pathway. The activity of the protein is regulated via its interaction with BETA CATENIN. Transcription factor 7-like 2 protein plays an important role in the embryogenesis of the PANCREAS and ISLET CELLS.Axin Signaling Complex: A specific complex of WNT SIGNALING PATHWAY proteins that mediates the phosphorylation-dependent destruction of cytosolic BETA-CATENIN. The complex is disrupted by cell surface binding of WNT PROTEINS, which allows beta-catenin levels to rise to the point where they migrate to the CELL NUCLEUS and activate transcription.Lymphoid Enhancer-Binding Factor 1: A T-cell factor that plays an essential role in EMBRYONIC DEVELOPMENT.Colonic Pouches: Sacs or reservoirs created to function in place of the COLON and/or RECTUM in patients who have undergone restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).Glycogen Synthase Kinases: A class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Wnt Signaling Pathway: A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, which when mutated results in the wingless phenotype, and the vertebrate INT gene, which is located near integration sites of MOUSE MAMMARY TUMOR VIRUS. The signaling pathway is initiated by the binding of WNT PROTEINS to cells surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome: The largest subunit of the anaphase-promoting complex. It acts primarily as a scaffold for the proper organization and arrangement of subunits. The C-terminal region of Apc1 contains a series of tandem amino acid repeats that are also seen in the 26S proteasome regulatory particle, and may assist with forming and stabilizing protein-protein interactions.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Colectomy: Excision of a portion of the colon or of the whole colon. (Dorland, 28th ed)Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Osteoma: A benign tumor composed of bone tissue or a hard tumor of bonelike structure developing on a bone (homoplastic osteoma) or on other structures (heteroplastic osteoma). (From Dorland, 27th ed)Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Genes, MCC: Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with the formation of colorectal cancer (MCC stands for mutated in colorectal cancer).Duodenoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the duodenum.Escherichia coli Infections: Infections with bacteria of the species ESCHERICHIA COLI.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Rectum: The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL.DNA, Neoplasm: DNA present in neoplastic tissue.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Wnt1 Protein: A proto-oncogene protein and member of the Wnt family of proteins. It is expressed in the caudal MIDBRAIN and is essential for proper development of the entire mid-/hindbrain region.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Mice, Inbred C57BLAmino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesTranscription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Cell Surface Extensions: Specialized structures of the cell that extend the cell membrane and project out from the cell surface.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.alpha Catenin: A catenin that binds F-ACTIN and links the CYTOSKELETON with BETA CATENIN and GAMMA CATENIN.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Pouchitis: Acute INFLAMMATION in the INTESTINAL MUCOSA of the continent ileal reservoir (or pouch) in patients who have undergone ILEOSTOMY and restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).Cell Line, Tumor: A cell line derived from cultured tumor cells.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Neoplasms, Multiple Primary: Two or more abnormal growths of tissue occurring simultaneously and presumed to be of separate origin. The neoplasms may be histologically the same or different, and may be found in the same or different sites.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Genes, Tumor Suppressor: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.Fibroma: A benign tumor of fibrous or fully developed connective tissue.HT29 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.Anticarcinogenic Agents: Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Anastomosis, Surgical: Surgical union or shunt between ducts, tubes or vessels. It may be end-to-end, end-to-side, side-to-end, or side-to-side.Neoplastic Syndromes, Hereditary: The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Wnt3A Protein: A Wnt protein subtype that plays a role in cell-cell signaling during EMBRYONIC DEVELOPMENT and the morphogenesis of the developing NEURAL TUBE.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Gastrointestinal Neoplasms: Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Epidermal Cyst: Intradermal or subcutaneous saclike structure, the wall of which is stratified epithelium containing keratohyalin granules.Hyperplasia: An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Desmoplakins: Desmoplakins are cytoskeletal linker proteins that anchor INTERMEDIATE FILAMENTS to the PLASMA MEMBRANE at DESMOSOMES.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Rectal Neoplasms: Tumors or cancer of the RECTUM.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Escherichia coli O157: A verocytotoxin-producing serogroup belonging to the O subfamily of Escherichia coli which has been shown to cause severe food-borne disease. A strain from this serogroup, serotype H7, which produces SHIGA TOXINS, has been linked to human disease outbreaks resulting from contamination of foods by E. coli O157 from bovine origin.Peutz-Jeghers Syndrome: A hereditary disease caused by autosomal dominant mutations involving CHROMOSOME 19. It is characterized by the presence of INTESTINAL POLYPS, consistently in the JEJUNUM, and mucocutaneous pigmentation with MELANIN spots of the lips, buccal MUCOSA, and digits.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.gamma Catenin: A multi-functional catenin that is highly homologous to BETA CATENIN. Gamma catenin binds CADHERINS and helps link their cytoplasmic tails to ACTIN in the CYTOSKELETON via ALPHA CATENIN. It is also found in DESMOSOMES where it mediates the link between DESMOSOMAL CADHERINS and DESMOPLAKIN.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Chromosome Deletion: Actual loss of portion of a chromosome.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.DNA Glycosylases: A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.Colitis, Ulcerative: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Stomach Neoplasms: Tumors or cancer of the STOMACH.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Abdominal NeoplasmsGastric Fundus: The superior portion of the body of the stomach above the level of the cardiac notch.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Cecal Neoplasms: Tumors or cancer of the CECUM.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Adenomatosis, Pulmonary: A neoplastic disease in which the alveoli and distal bronchi are filled with mucus and mucus-secreting columnar epithelial cells. It is characterized by abundant, extremely tenacious sputum, chills, fever, cough, dyspnea, and pleuritic pain. (Stedman, 25th ed)COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Jejunal Neoplasms: Tumors or cancer in the JEJUNUM region of the small intestine (INTESTINE, SMALL).Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Ampulla of Vater: A dilation of the duodenal papilla that is the opening of the juncture of the COMMON BILE DUCT and the MAIN PANCREATIC DUCT, also known as the hepatopancreatic ampulla.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Colorectal Neoplasms, Hereditary Nonpolyposis: A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.