Cyclin D1 Determines Androgen Dependent DNA Damage Sensing and Repair
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57867 | GEO | 2014/09/01
SECONDARY ACCESSION(S): PRJNA248292
REPOSITORIES: GEO
Similar Datasets
Project description:Murine prostate epithelial cells (PECs) were obtained from Ccnd1-/- and Ccnd1+/+ FvB mice (2-3 months of age). RNA extracted from PECs (3 technical replicates for each group) was labeled and used to probe Affymetrix 430_2.0 arrays. Three control Ccnd1+/+ PECs were compared to three Ccnd1+/+ PECs.
2014-09-01 | E-GEOD-57867 | biostudies-arrayexpress
Project description:Ovariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays. Six separate control Ccnd1+/+ C57BL/6 were compared to six Ccnd1-/- C57BL/6 mice. 3 mice in each group treated with placebo and three mice treated with E2
2013-07-16 | E-GEOD-48884 | biostudies-arrayexpress
Project description:Ovariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
2013-07-16 | GSE48884 | GEO
Project description:Therapy resistance and poor outcome in prostate cancer is associated with increased expression of cyclin D1. Androgens promote DNA double-strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclin D1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of ?H2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1 dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance.
| S-EPMC4715975 | biostudies-literature
Project description:The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein (pRb). It is known that cyclin D1 regulates ERα transactivation using heterologous reporter systems, the significance of this observation to E2 dependent gene activation is unknow. E2 stimulated MCF7 cells treated with cyclin D1 siRNA in order to analyze the genes regulated by estradiol in a cyclin D1 dependent manner. Hormone deprived MCF7 cells were treated with cyclin D1 siRNA or control siRNA and stimulated with E2 or vehicle
2013-07-18 | GSE48989 | GEO
Project description:The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein (pRb). It is known that cyclin D1 regulates ERM-NM-1 transactivation using heterologous reporter systems, the significance of this observation to E2 dependent gene activation is unknow. E2 stimulated MCF7 cells treated with cyclin D1 siRNA in order to analyze the genes regulated by estradiol in a cyclin D1 dependent manner. Hormone deprived MCF7 cells were treated with cyclin D1 siRNA or control siRNA and stimulated with E2 or vehicle Four separate 10cm plates of MCF7 cells treated with control siRNA were compared to four 10cm plates of MCF7 cells treated with cyclin D1 siRNA. 2 plates in each group treated with vehicle and two plates treated with E2.
2013-07-18 | E-GEOD-48989 | biostudies-arrayexpress
Project description:The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.
| S-EPMC1592725 | biostudies-literature
Project description:Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into nucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Ribonucleoprotein immunoprecipitation (RIP) analysis showed that MYF5 bound a subset of myoblast mRNAs; prominent among them was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking, and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. MYF5 silencing in proliferating growing myoblasts revealed that and MYF5 promoted CCND1 translation, and it also modestly increased transcription of Ccnd1 mRNA. Importantly, silencing MYF5 reduced myoblast growth as well as differentiation of myoblasts into myotubes, while overexpressing MYF5 in C2C12 cells upregulated CCND1 expression. We propose that MYF5 enhances early myogenesis in part by coordinately elevating Ccnd1 transcription and Ccnd1 mRNA translation.
2016-08-08 | GSE73704 | GEO
Project description:Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into nucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Ribonucleoprotein immunoprecipitation (RIP) analysis showed that MYF5 bound a subset of myoblast mRNAs; prominent among them was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking, and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. MYF5 silencing in proliferating growing myoblasts revealed that and MYF5 promoted CCND1 translation, and it also modestly increased transcription of Ccnd1 mRNA. Importantly, silencing MYF5 reduced myoblast growth as well as differentiation of myoblasts into myotubes, while overexpressing MYF5 in C2C12 cells upregulated CCND1 expression. We propose that MYF5 enhances early myogenesis in part by coordinately elevating Ccnd1 transcription and Ccnd1 mRNA translation. Four replicates were utilized from either Control (IgG) or MYF5-immunoprecipitated RNA samples from C2C12 cells growing in either growth medium (GM) or differentiation medium (DM) for a total of sixteen samples.
2016-08-08 | E-GEOD-73704 | biostudies-arrayexpress
Project description:Cyclin D1 is a cell cycle control protein that plays an important role in regenerating liver and many types of cancer. Previous reports have shown that cyclin D1 can directly enhance estrogen receptor activity and inhibit androgen receptor activity in a ligand-independent manner and thus may play an important role in hormone-responsive malignancies. In this study, we examine a distinct mechanism by which cyclin D1 regulates sex steroid signaling, via altered metabolism of these hormones at the tissue and cellular level. In male mouse liver, ectopic expression of cyclin D1 regulated genes involved in the synthesis and degradation of sex steroid hormones in a pattern that would predict increased estrogen and decreased androgen levels. Indeed, hepatic expression of cyclin D1 led to increased serum estradiol levels, increased estrogen-responsive gene expression, and decreased androgen-responsive gene expression. Cyclin D1 also regulated the activity of several key enzymatic reactions in the liver, including increased oxidation of testosterone to androstenedione and decreased conversion of estradiol to estrone. Similar findings were seen in the setting of physiological cyclin D1 expression in regenerating liver. Knockdown of cyclin D1 in HuH7 cells produced reciprocal changes in steroid metabolism genes compared with cyclin D1 overexpression in mouse liver. In conclusion, these studies establish a novel link between the cell cycle machinery and sex steroid metabolism and provide a distinct mechanism by which cyclin D1 may regulate hormone signaling. Furthermore, these results suggest that increased cyclin D1 expression, which occurs in liver regeneration and liver diseases, may contribute to the feminization seen in these settings.
| S-EPMC2907223 | biostudies-literature