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  • BRCA1
  • We aimed to assess whether CHEK2 was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in BRCA1 or BRCA2 had been identified. (biomedcentral.com)
  • Defects in one of two genes, breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2), put you at greater risk of developing both breast and ovarian cancer. (ndri.com)
  • Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2 . (springer.com)
  • The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. (asm.org)
  • The tumor suppressor gene BRCA1 is mutated in up to 50% of cases of familial early-onset breast cancer and in most families with hereditary breast and ovarian cancer ( 50 ). (asm.org)
  • Rad51 IRIF are reduced in BRCA1 -null cells ( 5 ). (asm.org)
  • BRCA1-deficient cells are hypersensitive to IR and DNA cross-linking agents, and the repair of both classes of lesions involves HR ( 5 , 16 , 41 , 53 ). (asm.org)
  • Loss of BRCA1 wild-type function in mouse embryonic stem (ES) cells leads to both reduced homology-mediated chromosomal plasmid integration and to decreased homologous repair of chromosomal DSBs induced by the site-specific I- Sce I endonuclease ( 40 , 41 , 55 ). (asm.org)
  • CHEK2
  • The gene CHEK2 encodes a checkpoint kinase playing a key role in the DNA damage pathway. (biomedcentral.com)
  • Though CHEK2 has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. (biomedcentral.com)
  • As part of an international breast cancer genetics study aiming to investigate candidate genes conferring an intermediate-risk of breast cancer, we mutation screened the coding exons and the adjacent proximal introns of CHEK2 in 1415 cases and 1204 controls. (biomedcentral.com)
  • subunits
  • In both yeasts and mammals, such controls operate primarily through transcriptional control of the levels of G 1 cyclins, which are unstable regulatory subunits of cyclin-dependent kinases (Cdk) required for G 1 exit ( 45 , 57 ). (asm.org)
  • functions
  • Our understanding of the important functions of p38 MAPK in the process of differentiation and cell death has grown considerably in the recent years and is now relatively established. (ijbs.com)
  • However disruption of the p38α gene results in embryonic death because of placental defects demonstrating that some functions cannot be compensated by other family members[ 3 - 6 ]. (ijbs.com)
  • The focus of this review is on the less characterized functions of the p38 MAPK pathway, such as its role in the regulation of cell cycle checkpoints and cell survival. (ijbs.com)
  • Importantly, all of these responses are detected in the nuclei of granule and Purkinje cells, suggesting that nuclear ATM functions in these cells similar to other cell types. (jneurosci.org)
  • transcription
  • Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann WK, Koeffler HP (2005) Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. (springer.com)
  • Genes regulated by Notch include helix-loop-helix inhibitory transcription factors of the Hes (Hairy/Enhancer of Split) and the Hey (Hairy/Enhancer of Split related with YRPW) families ( 8 , 9 ). (aacrjournals.org)
  • NF-κB refers to a family of transcription factors [p50, p65 (RelA), p52, RelB, c-Rel] that form homo- and heterodimers and regulate expression of various genes involved in proliferation and survival ( 10 ). (aacrjournals.org)
  • predisposition
  • Currently, women who carry mutations in high-risk breast cancer predisposition genes must make a difficult choice between regular surveillance, risk-reducing surgery, or taking part in trials of chemopreventive agents. (biomedcentral.com)
  • damage
  • Phosphorylated in response to DNA damage by the cell cycle checkpoint kinases ATR/ATM. (genecards.org)
  • We describe how p38 MAPK regulates both the G2/M as well as a G1/S cell cycle checkpoint in response to cellular stress such as DNA damage. (ijbs.com)
  • In response to stress stimuli that cause DNA damage, cells undergo cell cycle checkpoints to allow time for DNA repair. (ijbs.com)
  • In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. (frontiersin.org)
  • Exposure to tobacco smoke and to mutagenic xenobiotics can cause various types of DNA damage in lung cells, which, if not corrected by DNA repair systems, may lead to deregulation of the cell cycle and, ultimately, to cancer. (aacrjournals.org)
  • Exposure to tobacco smoke and to mutagenic xenobiotics causes various types of DNA damage to lung cells ( 1 ). (aacrjournals.org)
  • Finally, direct reversal of DNA damage, an unusual form of DNA repair, is also present in human cells. (aacrjournals.org)
  • We found that ATM is essentially nuclear in these cells and that various readouts of the ATM-mediated damage response are similar to those seen in commonly used cell lines. (jneurosci.org)
  • Living cells are continuously exposed to exogenous and endogenous agents that damage their DNA. (jneurosci.org)
  • We have reported that UCN-01 (7-hydroxystaurosporine) abrogates DNA damage-induced S and G 2 arrest and enhances cytotoxicity selectively in p53 mutant cells, thus providing a potential, tumor-targeted therapy. (aacrjournals.org)
  • The G 1 arrest is dependent upon wild-type p53 activity, whereas S and G 2 arrest do not require p53, so cells mutated for p53 (about 50% of tumors) arrest primarily in S or G 2 in response to damage. (aacrjournals.org)
  • DNA damage-induced, p53-activated neuronal cell death has already been identified in several neurodegenerative diseases. (springer.com)
  • expression
  • Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. (biomedcentral.com)
  • The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. (biomedcentral.com)
  • Using global gene profiling and argonaute-2 immunoprecipitation approaches, we showed that miR-195 regulates the expression of a number of cell cycle genes, including checkpoint kinase 1 (Chek1), which we identified as a highly conserved direct target of miR-195. (ahajournals.org)
  • Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1 , ATM , and other genes. (springer.com)
  • The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. (frontiersin.org)
  • Total RNA from cancer tissue of these patients was used to specify genes associated with altered per2 expression using the Human Cell Cycle RT 2 profiler PCR array system. (springer.com)
  • We identified seven genes positively correlated ( hus1 , gadd45α , rb1 , cdkn2a , cdk5rp1 , mre11a , sumo1 ) and two genes negatively correlated ( cdc20 , birc5 ) with per2 expression. (springer.com)
  • Expression of these seven genes was subsequently measured by real time PCR in all patients of the cohort. (springer.com)
  • We observed an increase in gene expression in cancer tissue compared to adjacent tissue in the first group of patients in all genes measured. (springer.com)
  • Expression of genes positively associated with per2 gene expression was dependent on tumor staging and changes were observed preferentially in cancer tissue. (springer.com)
  • For genes negatively associated with per2 expression we also detected changes in expression dependent on tumor staging. (springer.com)
  • The relevancy of gene expression for determination of diagnosis and prognosis should be considered in relation to tumor staging. (springer.com)
  • We synthesized interference plasmid targeted GINS2 successfully in vitro and also constructed recombinant adenovirus vector carrying GINS2 gene in order to down-regulate or up-regulate GINS2 expression from two aspects of positive and negative in APL. (medsci.org)
  • Further experiments revealed that down-regulation of GINS2 expression inhibited DNA replication and had a G2/M phase block in HL60 cells. (medsci.org)
  • On the contrary, after HL60 cells were infected by recombinant adenovirus vector which contained GINS2 gene, we observed that over-expression of GINS2 could promote HL-60 cell proliferation. (medsci.org)
  • In Arabidopsis thaliana , CAF-1 is important for the stable maintenance of gene expression states at shoot and root apical meristems ( 19 ). (asm.org)
  • Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c ( r = 0.54, P = 3.70 × 10 −8 and r = 0.73, P = 1.50 × 10 −65 , respectively). (aacrjournals.org)
  • Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. (aacrjournals.org)
  • Tumors which form in the rat bladder tumor model are similar at the level of gene expression to muscle invasive bladder tumors found in humans ( 11 ). (aacrjournals.org)
  • To explore the mechanism of the antitumor action of Iressa in the treatment of bladder tumors, we implemented a systems biology approach to characterize gene expression and pathway modulation in rat bladder tumors treated with Iressa. (aacrjournals.org)
  • Available evidence on expression of CycD genes in Arabidopsis is also consistent with their playing a role in response to external signals, with their major point of action occurring during G 1 . (asm.org)
  • PTEN
  • Amplification or upregulation of growth factor receptor tyrosine kinases and loss of the PTEN phosphatase are common events in gliomas and are considered signs of poor prognosis ( 11 ). (aacrjournals.org)
  • embryonic
  • We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. (mdpi.com)
  • tumors
  • This gene is one of four localized to a region of chromosome 17q23 where amplification occurs frequently in breast tumors. (genecards.org)
  • Leukemia is a malignant clone hematonosis deprived from hemopoietic stem cells, blood system malignant tumors account for about 7% of the new tumor patients each year. (medsci.org)
  • In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. (mdpi.com)
  • We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. (aacrjournals.org)
  • In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. (aacrjournals.org)
  • arrest
  • However, Gö6976 potently abrogated S and G 2 arrest and enhanced the cytotoxicity of the topoisomerase I inhibitor SN38 only in p53-defective cells. (aacrjournals.org)
  • Many cancer chemotherapy drugs currently in use ( e.g. , cisplatin, mitomycin C, camptothecin, and etoposide) are DNAdamaging agents and arrest cells in the G 1 , S, or G 2 phases of the cell cycle. (aacrjournals.org)
  • Cell cycle arrest protects cells from the toxicity of chemotherapeutic agents and insults such as ionizing radiation. (aacrjournals.org)
  • Despite its efficacy in cell culture, caffeine is not a viable choice as a clinical agent because the concentration required to abrogate arrest is far above the clinically achievable concentration. (aacrjournals.org)
  • Many plant cells arrest in G 1 in response to nutrient limitation or differentiation ( 12 ). (asm.org)
  • inhibit
  • Rather, an FKBP12-rapamycin complex is the toxic agent that then acts on another target to inhibit cell growth. (asm.org)
  • undergo
  • Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGF β and that these cells have an increased ability to form tumorspheres. (mdpi.com)
  • mitotic
  • This result led us to hypothesize that the cells were undergoing mitotic catastrophe, an abnormal mitosis that leads to eventual cell death. (aacrjournals.org)
  • Mitotic catastrophe is defined as abnormal mitosis that leads to eventual cell death. (aacrjournals.org)
  • in the latter case, cells exit mitosis into an aberrant interphase, characterized by the formation of multiple micronuclei, which can be used as a surrogate measure of mitotic catastrophe. (aacrjournals.org)
  • survival
  • Here we discuss the role of p38 MAPK in the mediation of cell cycle checkpoints and cell survival, processes that have received less attention. (ijbs.com)
  • Therefore, there is increasing interest in enhancing the radiosensitivity of lung cancer cells for development of effective therapies and improve patient survival with the added benefit of reduced systemic toxicity. (biomedcentral.com)
  • epithelial cells
  • The ductal approach to breast cancer, encompassing nipple aspiration, ductal lavage and duct endoscopy, allows assessment of breast ductal epithelial cells and their local microenvironment in a graded process of increasing invasiveness. (biomedcentral.com)
  • In the adult nonpregnant, nonlactating breast, fluid is secreted into the ducts and may contain exfoliated ductal epithelial cells along with foam cells, lymphocytes and neutrophils. (biomedcentral.com)
  • The intraduct approach is an umbrella term for several different techniques, including nipple aspiration (NA), ductal lavage (DL) and duct endoscopy (DE), that allow sampling of breast fluid and exfoliated epithelial cells - the cells at risk for malignant transformation. (biomedcentral.com)
  • The ductal approach is currently being evaluated as a reproducible method of gaining minimally invasive access to epithelial cells. (biomedcentral.com)
  • thus
  • It has also been linked to cell cycle checkpoint activation and cell death, and thus, alterations in this process can have wide-ranging biological consequences ( 4 ). (aacrjournals.org)
  • The intraduct approach, with its ability to examine directly those cells that are most at risk for malignant transformation and their surrounding milieu, intuitively offers the potential for refining personal risk estimates, thus aiding clinical management decisions, and it may facilitate detection of early breast cancer. (biomedcentral.com)
  • Plants therefore appear to be more similar to mammals than to yeasts in the operation of G 1 -to-S-phase control ( 1 , 20 ), and the plant homologs of D-type cyclins (CycD) are thus good candidates for influencing plant cell division in response to external conditions. (asm.org)
  • polymorphisms
  • We have therefore studied 102 single-nucleotide polymorphisms (SNP) in 34 key DNA repair and cell cycle control genes in 299 lung cancer cases diagnosed before the age of 50 years and 317 controls from six countries of Central and Eastern Europe. (aacrjournals.org)
  • lesion
  • The promutagenic lesion O 6 -methylguanine is repaired by such a process where a specific methyltransferase, encoded by the MGMT gene, transfers the methyl group from the DNA guanine residue to a cysteine residue located at its active site in an error-free process ( 6 ). (aacrjournals.org)