E-GEOD-35006
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA151175
PROVIDER: E-GEOD-35006 | ExpressionAtlas | 2015-08-18
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Profiling of p53-responsive genes in human breast cancer cells harboring endogenous ts-p53 E285K
| PRJNA151175 | ENA
Project description:The ts-p53 E285K protein is a rare p53 mutant with temperature-sensitive (ts) loss of function characteristics. In cancer cells, which express ts-p53 E285K intrinsically, endogenous wild type p53 activity is reconstituted by appropriate cultivation temperature (permissive condition). At non-appropriate cultivation temperature (restrictive condition) this p53 mutant is inactive. The present study took advantage of this mechanism and employed IPH-926 lobular breast cancer cells and BT-474 ductal breast cancer cells, which both harbor endogenous ts-p53 E285K, for the transcriptional profiling of p53-responsive genes. This new approach eliminated the need for genetic modification or cytotoxic stimulation to achive a p53 response in the cells being investigated . Three subseqent passages of IPH-926 lobular breast cancer cells (harboring ts-p53 E285K) were seeded into two parallel culture dishes each and were allowed to adopt to restrictive and permissive condition for 24 h before analysis on Affymetrix U133 Plus 2.0 microarrays. Subsequently, this experiment was repeated with BT-474 ductal breast cancer cells (also harboring ts-p53 E285K). To gate out non-specific temperature effects, the same experiment was also performed with MCF-7 breast cancer cells (harboring wt p53). Probe sets differentially expressed at restrictive versus permissive condition in MCF-7 were considered as non-specifically regulated. These probe sets were excluded from the final statistical analysis of IPH-926 and BT-474 expression data. response to restored p53 activity
2012-12-31 | E-GEOD-35006 | biostudies-arrayexpress
Project description:The ts-p53 E285K protein is a rare p53 mutant with temperature-sensitive (ts) loss of function characteristics. In cancer cells, which express ts-p53 E285K intriniscally, endogenous wild type p53 activity is reconstituted by appropriate cultivation temperature (permissive condition). At non-appropriate cultivation temperature (restrictive condition) this p53 mutant is inactive. The present study took advantage of this mechanism and employed IPH-926 lobular breast cancer cells and BT-474 ductal breast cancer cells, which both harbor endogenous ts-p53 E285K, for the transcriptional profiling of p53-responsive genes. This new approach eliminated the need for genetic modification or cytotoxic stimulation to achive a p53 response in the cells being investigated .
2012-12-31 | GSE35006 | GEO
Project description:Analysis of miRNA expression in human breast cancer samples with Agilent's miRNA arrays. These samples are part of a study where we have investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. We observed that indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Abstract of paper: Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. Indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these microRNAs silence anti-proliferative genes, which themselves are E2F1 targets. Thus, microRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative microRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Together these findings position microRNAs as novel key players in the mammalian cellular proliferation network. Keywords: Breast Cancer, miRNA, p53. 18 Primary human breast cancer samples analyzed for their miRNA expression. From two to four replicates were performed for each sample. Quality check (QC) were performed with Feature Extraction 9.1.3.44 and arrays not passing QC were excluded
2008-09-22 | E-GEOD-12848 | biostudies-arrayexpress
Project description:The tumor suppressor gene p53 is frequently mutated in human breast cancer and is a marker for poor prognosis and resistance to chemotherapy. Transplantation of p53-null mouse mammary epithelium into syngeneic wild-type mice leads to normal mammary gland development followed by spontaneous mammary tumors that recapitulate many of the phenotypic, molecular, and genetic features of human breast cancer. Using this genetically engineered mouse model, we have examined the molecular mechanisms underlying tamoxifen-dependent tumor prevention. To determine whether the changes observed in the ERα cistrome after tamoxifen exposure are reflected in changes in estrogen responsive gene signatures in p53-null mammary epithelial cells (MECs), we performed global gene expression analysis by microarray profiling of MECs isolated from control and tamoxifen-exposed mice 4 weeks after tamoxifen withdrawal and treated with E2 for 8h. We identified 245 differentially regulated genes (P<0.01 and FC>1.4). Of these, 177 genes (72%) were persistently upregulated and 68 genes (28%) were persistently downregulated after transient exposure to tamoxifen. These results indicate that transient exposure to tamoxifen leads to lasting intrinsic changes in gene expression profiles of p53-null mammary epithelial cells that persist after tamoxifen withdrawal.
2018-04-17 | GSE77948 | GEO
Project description:Mutations in the TP53 gene are the most common genetic alterations in breast cancer. To investigate at a single cell level what is the gene expression network that is regulated by mutant p53 at a non-tumoral stage, we employed a pre-neoplastic mouse model harboring the germline hotspot missense mutation R172H. We thus performed scRNAseq of cells derived from the normal mammary glands of mice harboring wt or mutant p53.
2023-10-06 | GSE239706 | GEO
Project description:TP53 is one of the most frequently mutated gene in breast cancer. While p53 mutations often lead to loss of wild-type p53 activity, they can have a wide variety of gain-of-function (GOF) consequences. The impact of these GOF mutations in p53 on the anti-tumor immune response in breast cancer remains elusive. To address this, we have generated mouse mammary tumor models based on orthotopic injection of isogenic cell lines harboring the p53 mutations that most frequently occur in human breast cancer. By comparing the tumor immune landscape of these models and human breast tumors, we have uncovered that specific p53 point mutants consistently induce an immunologically ‘hot’ tumor phenotype, characterized by high infiltration of cytotoxic T cells, while other p53 mutations induce a non-T cell inflamed (‘cold’) microenvironment. In accordance with these high T cell levels, the hotp53 mutant tumors respond better to anti-PD-1immune checkpoint blockade than cold p53 mutant tumors. By comparing the different p53 mutants in terms of proteome profile, chromatin bindingproperties and protein complex formation, we have uncovered that T cell-enriched p53 mutants activate autophagy. Disruption of autophagy in an immunologically hot p53 mutant tumor abrogated the response to anti-PD-1 therapy. This work demonstrates that not all p53 mutations shape the immune microenvironment of mammary tumors in a similar fashion, and that response to immune checkpoint blockade depends on specific mutations in p53. This argues that screening for specific p53 aberrations in breast cancer may help guide immunotherapeutic strategies.
2023-09-08 | GSE155639 | GEO
Project description:Analysis of miRNA expression in human breast cancer samples with Agilent's miRNA arrays. These samples are part of a study where we have investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. We observed that indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Abstract of paper: Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcription regulators, E2F and p53, their targets, and a family of 14 microRNAs. Indicative of their significance, expression of these microRNAs is down-regulated in senescent cells and in breast cancers harboring wild-type p53. These microRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these microRNAs silence anti-proliferative genes, which themselves are E2F1 targets. Thus, microRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative microRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Together these findings position microRNAs as novel key players in the mammalian cellular proliferation network. Keywords: Breast Cancer, miRNA, p53.
2008-09-23 | GSE12848 | GEO
Project description:More than two thirds of breast cancers express the estrogen receptor (ER) and depend on estrogen for growth and survival. Therapies targeting ER function including aromatase inhibitors that block the production of estrogens and ER antagonists that alter ER transcriptional activity play a central role in the treatment of ER+ breast cancers of all stages. In contrast to ER- breast cancers, which frequently harbor mutations in the p53 tumor suppressor, ER+ breast cancers are predominantly wild type for p53. Despite harboring wild type p53, ER+ breast cancer cells are resistant to chemotherapy-induced apoptosis in the presence of estrogen. Using genome-wide approaches we have addressed the mechanism by which ER antagonizes the pro-apoptotic function of p53. Interestingly both ER agonists such as estradiol and selective ER modulators (SERM) such as tamoxifen promote p53 antagonism. In contrast the full ER antagonist fulvestrant blocks the ability of ER to inhibit p53-mediated cell death. This suggests an improved strategy for the treatment of ER+ breast cancer utilizing antagonists that completely block ER action together with drugs that activate p53-mediated cell death. MCF7 cells were hormone-depleted for 3 days and then treated with 10 uM doxorubicin for 12 hours
2012-11-02 | E-GEOD-39870 | biostudies-arrayexpress