The future promises to yield new discoveries and advances in our understanding of cardiomyocyte cell cycle regulation that will hopefully give rise to the ability to promote regenerative myocardial growth. With respect to the intrinsic proliferative and de novo cardiomyogenic potential of the adult heart, it is abundantly clear from studies cited herein that the published values for the magnitude of both processes vary dramatically. It is very important to rigorously determine the extent to which these processes do occur. If the intrinsic rates for cardiomyocyte proliferation and/or de novo cardiomyogenic differentiation are exceedingly low, then the ability to exploit these processes for clinical benefit would likely be quite limited. Increasing the frequency of these events would require the existence, identification, and ultimately the successful delivery of cytokines that normally regulate the process. Conversely, if these processes do occur at the frequency that some studies suggest, then ...
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TY - JOUR. T1 - Interaction between the pRb2/p130 C-terminal domain and the N-terminal portion of cyclin D3. AU - Bonetto, Francesco. AU - Fanciulli, Maurizio. AU - Battista, Tullio. AU - De Luca, Antonio. AU - Russo, Patrizia. AU - Bruno, Tiziana. AU - De Angelis, Roberta. AU - Di Padova, Monica. AU - Giordano, Antonio. AU - Felsani, Armando. AU - Paggi, Marco C.. PY - 1999/12/15. Y1 - 1999/12/15. N2 - An association between cyclin D3 and the C-terminal domain of pRb2/p130 was demonstrated using the yeast two-hybrid system. Further analysis restricted the epitope responsible for the binding within the 74 N-terminal amino acids of cyclin D3, independent of the LXCXE amino acid motif present in the D-type cyclin N-terminal region. In a coprecipitation assay in T98G cells, a human glioblastoma cell line, the C-terminal domain of pRb2/p130 was able to interact solely with cyclin D3, while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous ...
The protein encoded by the Bcl-1 oncogene, known as cyclin D1, belongs to the highly conserved family of cyclin-dependent kinase (CDK) regulators. It is also known as CCND1, B-cell lymphoma 1 protein (BCL1), parathyroid adenomatosis 1 (PRAD1), B-cell CLL/lymphoma 1, G1/S-specific cyclin-D1, D11S287E, and U21B31. Different cyclins exhibit distinct expression and degradation patterns that contribute to the coordination of the cell cycle during mitosis. Cyclin D1 interacts with CDK4 and CDK6, whose activity is required for the cell cycle G1/S transition. Cyclin D1 also interacts with tumor suppressor protein Rb. Mutations in the Bcl-1 gene are associated with a variety of cancers, including esophageal, breast, and bladder cancer, as well as a variety of B-cell-related leukemias and lymphomas.. ...
and a shift of cyclin D1 mRNA from the polysome-associated to free mRNA fraction, indicating that 15d-PGJ2 inhibits the initiation of cyclin D1 mRNA translation. The selective rapid decrease in cyclin D1 protein accumulation is facilitated by its rapid turnover (t1/2=34 min) after inhibition of cyclin D1 protein synthesis. The half-life of cyclin D1 protein is not significantly altered in cells treated with 15d-PGJ2. Treatment of cells with 15d-PGJ2 results in strong induction of heat shock protein 70 (HSP70) gene expression, suggesting that 15d-PGJ2 might activate protein kinase R (PKR), an eIF- ...
The alternatively spliced cyclin D1b variant of the CCND1 gene has been proposed to have higher oncogenic potential than cyclin D1a (8, 9). In breast cancer, aberrant cyclin D1b expression confers resistance to therapeutic treatment (30) and is associated with poor prognosis in patients (31). Cyclin D1b was also recently shown to enhance cell invasiveness and anchorage-independent growth of bladder cancer cells (32), and this isoform has been detected in various other cancer types (8, 28, 33). In PCa, changes in the cyclin D1b/cyclin D1a ratio are of particular relevance. Indeed, whereas both isoforms support cell cycle progression, they behave differently in the interaction with the AR pathway. Cyclin D1a was reported to associate with AR and to negatively regulate its transcriptional activity, thereby representing a brake for uncontrolled proliferation of PCa cells (6). By contrast, this negative feedback function is lacking in cyclin D1b (11), and its expression positively correlated with PCa ...
购买经敲除验证的重组Cyclin D1兔单克隆抗体[EP272Y](ab40754),Cyclin D1抗体经WB,IP验证,可与人,小鼠,大鼠样本反应。8篇文献引用,4个独立用户反馈。
Plasmid pIS1 Cyclin D2 short UTR from Dr. David Bartels lab contains the insert Cyclin D2 short UTR and is published in Cell. 2009 Aug 21. 138(4):673-84. This plasmid is available through Addgene.
Cyclin D1 expression is induced by Sox17.(A-B) Immunohistochemistry for cyclin D1 was performed on lung sections from adult CCSPrtTA (A) and CCSPrtTA/tetO-Sox
Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-third of these cases, this is linked to amplification of the 11q13 chromosomal region, which also includes the CCND1 gene. These tumors are predominantly estrogen receptor-positive, and for this reason, these patients are often selected for adjuvant antiestrogen therapy. No information is available, however, as to whether cyclin D1 overexpression due to gene amplification might interfere with and reduce antiestrogen efficacy. This was investigated here by taking advantage of an experimental model that reproduces cyclin D1 overexpression resulting from increased CCND1 gene dosage in hormone-responsive human ...
THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues.
Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence ...
FIG.9. Effects of UV stimulation on cyclin D1 and p52. (A) UV treatment down regulates cyclin D1 protein levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Whole-cell lysates were prepared and immunoblotted for cyclin D1 and a β-actin control as indicated. (B) UV treatment inhibits the cyclin D1 promoter in a manner dependent upon the proximal κB element. One and a half micrograms of each of the cyclin D1 (−66) and cyclin D1 (−66 mut) luciferase reporter plasmids were transfected into U-2 OS cells. Cells were treated with 40-J/m2 UV radiation for 6 h as indicated. Results are expressed as change in activation or repression (n-fold) relative to levels seen in the relevant untreated cell controls. luc, luciferase. (C) UV treatment induces Ser-15 phosphorylated endogenous p53 and down regulates Bcl-3 levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Nuclear protein extracts were prepared and immunoblotted for p53, ...
Metabolism of L-Arg by arginase I-producing MDSCs leads to a significant decrease in the extracellular levels of L-Arg in murine tumor models and in patients with cancer (5, 25). The decreased levels of L-Arg induced the prolonged loss in the expression of CD3ζ (7, 26) and inhibited T cell proliferation (8). These effects were not associated with the induction of apoptosis and were rapidly reversible after replenishment of L-Arg or citrulline (8). We recently showed that activated primary T cells cultured in the absence of L-Arg were arrested in the G0-G1 phase of the cell cycle (8). The G0-G1 arrest in the cell cycle observed in L-Arg-deprived T cells correlated with an inability to upregulate the expression of cyclin D3 (8). Results from cyclin D3 knockout mice had demonstrated that cyclin D3 is essential for the maturation of T cells in the thymus (27), and they suggested a potential and selective role in T cell proliferation. Additionally, silencing of cyclin D3 induced a similar inhibition ...
As described above, we have reported a new physiological function of Cyclin D2 in the neuronal development of the mouse. We next questioned whether this mechanism is conserved among mammalian species. In humans, we found an accumulation of Cyclin D2 protein at the basal side of the cortical primordium at gestation week 16 (Tsunekawa et al. 2012). We also noted that the cis-acting element identified in mice that promotes basal transportation is highly conserved in human (74% match in the National Center for Biotechnology Information [NCBI] database). Therefore, it is tempting to speculate that in the human cortical primordium, Cyclin D2 mRNA is similarly transported within the basal process toward the basal endfoot and locally translated into protein. Notably, the basal transport cis-element that we have identified appears to be unique to mammals, as similar sequences are not found in avians or amphibians (NCBI database). Similarly, no accumulation of Cyclin D2 mRNA in the basal side of the chick ...
D-type cyclins (cyclin D1, D2 and D3) are components of the core cell cycle machinery. Rearrangements of cyclin D genes and overexpression of cyclin D proteins...
...(PHILADELPHIA) Cyclin D1 a protein that helps push a replicating cel... In addition to its role in regulating the cell cycle cyclin D1 induc...Using antisense RNA Dr. Pestells group was the first to show that cy...In the current study the group sought to investigate the mechanism by...,Cyclin,D1,governs,microRNA,processing,in,breast,cancer,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Smad nuclear interacting protein 1 (SNIP1) is an evolutionarily conserved protein containing a forkhead-associated (FHA) domain that regulates gene expression through interactions with multiple transcriptional regulators. Here, we have used short interfering RNAs (siRNAs) to knockdown SNIP1 expression in human cell lines. Surprisingly, we found that reduction in SNIP1 levels resulted in significantly reduced cell proliferation and accumulation of cells in the G1 phase of the cell cycle. Consistent with this result, we observed that cyclin D1 protein and mRNA levels were reduced. Moreover, SNIP1 depletion results in inhibition of cyclin D1 promoter activity in a manner dependent upon a previously characterized binding site for the AP-1 transcription factor family. SNIP1 itself is induced upon serum stimulation immediately prior to cyclin D1 expression. These effects were independent of the tumour suppressors p53 and retinoblastoma (Rb), but were consistent with an interaction with BRG1, a component of
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
The cyclin D1 expression pattern is not altered by signaling inhibitors. If the PI3K/AKT/GSK3 pathway stabilizes cyclin D1 levels specifically during G1 and G2 phases as suggested above, inhibitors of this pathway would produce a reduction in cyclin D1 expression during these cell cycle phases to the low levels seen during S phase. Thus, inhibition of these signaling pathways would be expected to result in low, uniform expression of cyclin D1 throughout the cell cycle. PI3K was inhibited by LY294002, while the kinase mTOR was inhibited by rapamycin in actively cycling human diploid fibroblast (MRC5) cultures. After 2 hrs treatment, including a terminal pulse with BrdU, the culture was fixed and stained with fluorescent antibodies against both cyclin D1 and BrdU, while DNA was stained with DAPI. Individual images of each fluorochrome were collected with a sensitive CCD camera, and subjected to image analysis to accurately quantitate the level of each fluorochrome in each cell (see [20]). The ...
Citation: Soni R. and Chaudhuri B. (2001) Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over-expression of Bcl-2 and cyclin D1. International Journal of Oncology. 18 (5) pp.1035-40 ...
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View mouse Ccndbp1 Chr2:121008403-121016904 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
its induction represents a mechanism by which myeloma cells can induce cyclin D2 dysregulation, and contribute to disease pathogenesis ...
Cyclin D1 is a G1-specific cyclin that has been linked to lymphoid, parathyroid, and breast tumors. Recent studies suggested that high protein levels of cyclin D1 are not always produced when cyclin D1 mRNA is overexpressed in transfected cells, suggesting that posttranscriptional events may be important in cyclin D1 regulation. The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF-4E]) is a potential regulatory of several posttranscriptional events, and it can itself induce neoplastic transformation. Consequently, we examined eIF-4E as a potential regulator of cyclin D1. Overexpression of cyclin D1 mRNA in NIH 3T3 cells did not increase cyclin D1 protein. In contrast, overexpression of eIF-4E markedly increased the amount of cyclin D1 protein in NIH 3T3 cells. This increase was specific to cyclin D1 in comparison with the retinoblastoma gene product, c-Myc, actin, and eukaryotic initiation factor 2 alpha. We also examined cyclin D1 protein in cells expressing an estrogen ...
Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties with regard to the cellular migration function of cyclin D1. Whereas they displayed little difference in transcriptional co-repression assays on idealized reporter genes, microarray cDNA expression analysis revealed differential regulation of genes including those that influence cellular migration. Additionally, while cyclin D1a stabilized p27KIP1 and inhibited RhoA-induced ROCK kinase
The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. Expression of the members of this family of cyclins, D1, 2 and 3, is spatially and temporally regulated with respect to growth factor receptor ligation. Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in T-cells. Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction endonuclease digestion and a sub-clone extending 1.7kb upstream of exon 1 was sequenced and studied. The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. Transient ...
Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Hudson, J., Mills, R., Titmarsh, D., Koenig, X., Parker, B., Ryall, J., Quaife-Ryan, G., Voges, H., Hodson, M., Ferguson, C., Drowley, L., Plowright, A., Wang, Q., Gregorevic, P., Xin, M., Thomas, W., Parton, R., Nielsen, L., Launikonis, B., James, D., Elliott, D. and Porrello, E. (2017). Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Abstracts for the 65th Cardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research Australasian Section Annual Scientific Meeting, Perth, Australia, 10 - 13 August 2017. Chatswood, NSW, Australia: Elsevier. doi: 10.1016/j.hlc.2017.06.375. ...
TY - JOUR. T1 - Prognostic role of cyclin d1 in lung cancer relationship to proliferating cell nuclear antigen. AU - Caputi, Mario. AU - Groeger, Angela M.. AU - Esposito, Vincenzo. AU - Dean, Charity. AU - De Luca, Antonio. AU - Pacilio, Carmen. AU - Muller, Michael R.. AU - Giordano, Giovan G.. AU - Baldi, Feliciano. AU - Wolner, Ernst. AU - Giordano, Antonio. PY - 1999. Y1 - 1999. N2 - We developed an immunohistochemical assay specific for cyclin D1 and suitable for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed ...
Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G1→S cell cycle phase transition and development and progression in carcinogenesis. Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. In our continuing studies on the mechanism of prostate cancer prevention by resveratrol, focusing on the role of its recently discovered target protein, quinone reductase 2 (NQO2), we generated NQO2 knockdown CWR22Rv1 using short hairpin RNA (shRNA)-mediated gene silencing approach. We found that, compared with cells expressing NQO2 (shRNA08), NQO2 knockdown cells (shRNA25) displayed slower proliferation and G1 phase cell accumulation. Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. Moreover, shRNA25 cells showed a 37% ...
The relative levels of cyclin D1 (CCND1) (a) and (b) transcripts were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and found to vary according to the tissue origin in both control and tumor samples. A five-fold overexpression of both isoforms was observed in 28/38 cases of mantle cell lymphoma (MCL) and of only one isoform in 10/38 MCL. No correlation was observed between expression of cyclin D1 isoforms and CCND1 genotype at position 870. ...
Cell proliferation is regulated by the balance between cyclin-dependent kinases (CDKs) and CDK inhibitors such as p27. In neonatal cardiomyocytes, p27 is a key inhibitor of cell proliferation (6) and cyclin D1 is important for cell cycle progression (36). To delineate the pathway through which TIMP-3 inhibits neonatal cardiomyocyte proliferation, the effect of TIMP-3 on cyclin D1 and p27 expression was investigated. Our data showed that cyclin D1 was increased in TIMP-3−/− cardiomyocytes and decreased in rTIMP-3-treated cells as compared with WT. Consistent with these results, p27 expression was decreased in the TIMP-3−/− cardiomyocytes and neonatal hearts as compared with WT. This decrease in p27 expression resulted in an increase in cardiomyocyte proliferation both in vitro and in vivo. Furthermore, treatment of cardiomyocytes with rTIMP-3 resulted in a significant increase in p27 expression, which led to a significant decrease in cardiomyocyte proliferation. Our data suggest that ...
Home » meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish ...
Mouse Monoclonal Anti-Cyclin D1 Antibody (DCS-6). G1-Cyclin & Mantle Cell Marker. Validated: WB, ELISA, Flow, ICC/IF, IHC-Fr, IHC-P, IP, PAGE. Tested Reactivity: Human, Mouse, Rat, and more. 100% Guaranteed.
Monoclonal clone# G2 antibody for CYCLIN D2/CCND2 detection. Host: Mouse.Size: 100μg/vial. Tested applications: ICC. Reactive species: Human. CYCLIN D2/CCND2 information: Molecular Weight: 32826 MW; Subcellular Localization: Nucleus . Cytoplasm . Membran
Proliferation is accelerated in GSK3β inhibitor treated mice compared to similarly injured, but vehicle treated micea) Cyclin D1, c-myc and β-catenin levels b
In contrast to cyclin D1 and D2, the expression level of cyclin D3 was high in the hindbrain at the E15.5 stage (Figure 3I, arrowhead). Moreover, in the midbrain cyclin D3 was expressed in cells closer to the ventricle than those expressing cyclin D2 (Figure 3H, I, arrows).. Discussion. At the E10.5 stage, all three D-type cyclins were expressed in most of the spinal cord cells but cyclin D1 and D3 showed higher expression levels in the dorsal half of the spinal cord. Wianny et al. (1998) found that the dorso-ventral gradient of the cyclin D1 transcript also occurs in the spinal cord of 7-9 somite-stage embryos. However, in our study we found that at the E10.5 stage cyclin D2 was not missing from the floor plate and also that cyclin D3 was not expressed only ventrally, as was reported for the transcripts of the genes in 7-9 somite stage embryos by Wianny et al. (1998). This may have been due to altered expression patterns of these genes during the time course of spinal cord development and ...
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
The findings herein advance a strategy for inducing myocardial repair in pediatric patients. Myocardial regeneration experiments in neonatal mice were not feasible until the recent introduction of techniques for inducing myocardial injury (15, 17, 41). LAD ligation (16, 17) and amputation injury (15, 42) in neonatal mice were reported to lead to scarless repair, although these results are controversial (43, 44). Here, we verify that cryoinjury is a technically feasible method that produces scar formation and dysfunction, which is in line with the scar formation and delayed repair process observed in zebrafish (31-33) and neonatal mice (35, 36) after cryoinjury. We also show that cryoinjury in neonatal mice is a useful model for human infants with heart disease because it recapitulates the scar formation, dysfunction, and decrease in cardiomyocyte cell cycle activity frequently seen in young patients with heart disease. The observed decrease in cardiomyocyte proliferation after cryoinjury ...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 ...
B78 Growth arrest represents an innate barrier to carcinogenesis. DNA damage and replicational stress are known to induce growth arrest and apoptotic death to avert genomic instability and consequently carcinogenesis. Working on the genotoxic stress induced by hydroxyurea and methylmethanesulfone, we observed a growth arrest at G1/S-phase that was mediated by destabilization of cyclin D1. The growth arrest was independent of the stability of cdc25A and preceded transcriptional up-regulation of p21waf1. Cyclin D1 destabilization involved its phosphorylation by GSK-3beta at threonine-286 since overexpression of the kinase-dead mutant of GSK-3beta or cyclin D1T286A mutant conferred stability to cyclin D1. Further, overexpression of cyclin D1T286A also helped in bypassing G1/S phase growth arrest. We also observed a rapid inactivation of Akt/PKB kinase in the presence of hydroxyurea. Enforced expression of the constitutively active Akt or viral oncoprotein HBx was sufficient to overcome growth ...
Sigma-Aldrich offers abstracts and full-text articles by [Diana C Canseco, Wataru Kimura, Sonia Garg, Shibani Mukherjee, Souparno Bhattacharya, Salim Abdisalaam, Sandeep Das, Aroumougame Asaithamby, Pradeep P A Mammen, Hesham A Sadek].
Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of
Severe and prolonged cytopenias represent a considerable problem in clinical stem cell transplantations. Cytokine-induced ex vivo expansion of hematopoietic stem and progenitor cells has been intensively explored as a means of accelerating hematopoietic recovery following transplantation but have so far had limited success. Herein, overexpression of D-type cyclins, promoting G0/G1 to S transition, was investigated as an alternative approach to accelerate myeloid reconstitution following stem cell transplantation. With the use of retroviral-mediated gene transfer, cyclin D2 was overexpressed in murine bone marrow progenitor cells, which at limited doses showed enhanced ability to rescue lethally ablated recipients. Competitive repopulation studies demonstrated that overexpression of cyclin D2 accelerated myeloid reconstitution following transplantation, and, in agreement with this, cyclin D2-transduced myeloid progenitors showed an enhanced proliferative response to cytokines in vitro. Furthermore,
Although mutations that activate the Hedgehog (Hh) signalling pathway have been linked to several types of cancer, the molecular and cellular basis of Hhs ability to induce tumour formation is not well understood. We identified a mutation in patched (ptc), an inhibitor of Hh signalling, in a genetic screen for regulators of the Retinoblastoma (Rb) pathway in Drosophila. Here we show that Hh signalling promotes transcription of Cyclin E and Cyclin D, two inhibitors of Rb, and principal regulators of the cell cycle during development in Drosophila. Upregulation of Cyclin E expression, accomplished through binding of Cubitus interruptus (Ci) to the Cyclin E promoter, mediates the ability of Hh to induce DNA replication. Upregulation of Cyclin D expression by Hh mediates the distinct ability of Hh to promote cellular growth. The discovery of a direct connection between Hh signalling and principal cell-cycle regulators provides insight into the mechanism by which deregulated Hh signalling promotes ...
BACKGROUND: To investigate markers for predicting breast cancer progression, we performed a candidate gene-based study that assessed expression change of three genes, cyclin D1, β-catenin, and metastasis-associated protein-1 (MTA1), involving in aggressive phenotypes of cancerous cells, namely hyperproliferation, epithelial-mesenchymal transition, and global transcriptional regulation.. METHODS: Specimens were from 150 enrolled female patients, with invasive ductal carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, β-catenin, and MTA1 in cancerous and noncancerous cells microdissected from the primary tumor site was determined by quantitative real-time PCR. The relationship between mRNA expression levels of the genes and clinicopathologic features was assessed by statistical analysis. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox regression model.. RESULTS: Cyclin D1 was shown to be ...
We report several novel observations. First, we find that multiple cdk4/6 and D-cyclin combinations can robustly stimulate human β-cell replication in vitro. Surprisingly, among all of the possible cdk4/6-D-cyclin combinations, cyclin D3 appeared to be a particularly effective partner for cdk6 and cdk4. Second, we demonstrate that, although cyclin D2 is a very effective partner for both cdk4 and cdk6 in stimulating human β-cell replication, and despite its being both present and essential for rodent β-cell replication and function, it is only marginally detectable in human β-cells. Third, we observe that the D-cyclins and cdks 4 and 6 are principally cytosolic proteins in the human β-cell. Fourth, we report that a single member of the cdk4/6 D-cyclin complex, cdk6, is able to enhance human β-cell transplantation in vivo. Fifth, we demonstrate that human β-cell replication can be sustained in vivo for at least four weeks using cdk6.. The rapid proliferation induced by the D3 combinations ...