E-GEOD-31812
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA145251
PROVIDER: E-GEOD-31812 | ExpressionAtlas | 2015-08-17
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-31812-analysis-methods.tsv | Tabular | |||
| E-GEOD-31812-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-31812-configuration.xml | Xml | |||
| E-GEOD-31812-percentile-ranks.tsv | Tabular | |||
| E-GEOD-31812.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 53 |
Similar Datasets
Project description:Mutant p53 Disrupts Mammary Acinar Morphogenesis via the Mevalonate Pathway
| PRJNA145251 | ENA
Project description:p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors. Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53.
2012-02-13 | GSE31812 | GEO
Project description:p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors. Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53. RNA was isolated from three independent experiments of MDA-468.shp53 cells cultured under 3D conditions for 8 days in the presence or absence of DOX, reversed transcribed and hybridized to an Affymetrix GeneChip expression array. Data was processed using the Robust Multichip Average (RMA) algorithm to give expression signals and paired t-test was applied for each probe. Probes with 1% significance were selected for Ingenuity Pathway Analysis.
2012-02-13 | E-GEOD-31812 | biostudies-arrayexpress
Project description:In human breast cancer, mutations in the p53 gene are associated with poor prognosis, suggesting a mutant p53 “gain of function”. To study this phenomenon, we co-expressed mutant p53R270H in mice in which SV40 early proteins initiate the development of mammary adenocarcinomas in descendants of mammary epithelial cells that survived involution (WAPT-mice). This model allows the characterization of mammary carcinomas that developed in the absence or presence of mutant p53, while the endogenous wild-type p53 is functionallycompromised. Co-expression of mutant p53 significantly aggravated the phenotype of bitransgenic mice, as evidenced by a higher tumor incidence, a worse clinical staging and histological grading, as well as an enhanced invasiveness of the tumors, and more frequent pulmonary metastasis. Our data indicate that mutant p53 does not exert this effect by increasing genomic instability. On the contrary, lower grade tumors in WAP-T mice generally accumulated more amplifications of pro-survival genes than the corresponding tumors in bitransgenic animals, suggesting that mutant p53 can compensate for such genetic alterations by alternative mechanisms, possibly by its transcriptional activities, and thereby facilitate tumor formation. As a common feature and associated with their enhanced invasiveness, high grade tumors showed high level amplification of the Met-locus. Keywords: mutant p53, SV40 early proteins, tumor progression, tumor grade, tumor stage, mammary carcinoma, animal model, Met
2007-12-31 | GSE7135 | GEO
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
2018-10-25 | PXD003120 | Pride
Project description:Purpose: discover the downstream pathways and the mechanism of target activation by the p53:Myc axis in normal mammary and cancer stem cells Methods: we performed ChIPseq experiments from NMuMG cells grown in adhesion under standard conditions Results: the p53:Myc axis orchestrates its transcriptional response in mammary-epithelial cells via a dual and overlapping mechanism: i) a tightly controlled epistasis driven by p53 and executed by Myc, and ii) a co-operative double occupancy of their downstream effectors at different regulatory regions
2019-01-21 | GSE87002 | GEO
Project description:Upon induction, WAP-T mice express two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens in the mammary epithelium, recapitulating thereby the loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated (respectively low- and high-grade) mammary adenocarcinomas. We here studied the postulated mutant p53 (mutp53) 'gain of function' during mammary tumor development, progression and metastasis by crossing WAP-T mice with mutant p53 transgenic WAP-mutp53 mice.
2013-12-18 | GSE53395 | GEO
Project description:We compared the expression levels of X-linked genes in the mammary glands of Brca1 D11/D11;p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle: virgin, pregnant day 16.5, and lactation day 1, using a cDNA microarray. In about 690 X-linked genes that are expressed at these three stages of mammary cycle of development, we found 16 X-linked genes showed altered expression levels in Brca1 D11/D11;p53+/- mammary glands in comparison with controls at all three time points. Among them, 9 genes were up-regulated and 7 were down-regulated. This result indicates that mutation of Brca1 could affect expression of a few X-linked genes in mammary tissues. However, this was unlikely caused by failure of X chromosome inactivation, as seven of them were down-regulated, and Xist RNA was expressed in all the Brca1 mutant mammary tissues. Keywords: BRCA1 mutation analysis
2006-09-19 | GSE5861 | 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:The tumor suppressor transcription factor p53 is mutated in nearly 50% of all cancer cases, and this frequency increases with stage and resistance to therapy. Hotspot p53 mutations lose direct DNA binding activity while gaining oncogenic function. These structural p53 mutants can bind to new regions of the genome via interactions with other transcription factors. One example is the ETS transcription factor ETS2, which was previously reported to bind mutant p53. Yet, a comprehensive understanding of mutant p53 association with the ETS family needs to be understood. Here, we compare mutant p53 interaction across 26 ETS transcription factors. Mutant p53 bound ETS proteins better than wild-type p53. All ETS proteins tested bound to mutant p53 to some extent, yet relative binding differed. The ETS DNA binding domain provided a common interaction interface, but strong binding required a second interaction domain. Genome-wide mapping found that the ETS protein ERG could recruit mutant p53 to regulatory regions of genes necessary for morphogenesis, locomotion, and androgen response in prostate cancer cells. Lastly, ETS factors that interact strongly with mutant p53 tend to be upregulated in p53 mutant ovarian cancer. These results suggest that multiple ETS proteins can work with mutant p53 in cancer.
2024-06-28 | GSE270925 | GEO