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Expression of mutant p53 in Mammary carcinomas in WAP-SV40 transgenic mice

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE53395 | GEO | 2013/12/18

SECONDARY ACCESSION(S): PRJNA231914

REPOSITORIES: GEO

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Expression of mutant p53 in Mammary carcinomas in WAP-SV40 transgenic mice

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. This study includes gene expression analysis of 12 high grade mammary carcinoma samples. An alternative probe set mapping published by the AffyProbeMiner project (remapped transcript consistent cdf-file) was used to calculate probe set signals of 6 mono-trangenic WAP-T-NP8 samples from the dataset GSE29117 and 6 bi-transgenic WAP-T-NP8 x WAP-W10 (mutp53R245R) samples.

2013-12-18 | E-GEOD-53395 | biostudies-arrayexpress

Mammary carcinomas in WAP-SV40 transgenic mice [aCGH]

Project description:Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates 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 mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis. CGH analysis of 15 mammary carcinoma samples of the NP8 WAP-SV40 mouse line.

2012-10-31 | E-GEOD-31097 | biostudies-arrayexpress

Mammary carcinomas in WAP-SV40 transgenic mice [aCGH]

2012-10-31 | GSE31097 | GEO

Mammary carcinomas in WAP-SV40 transgenic mice [gene expression]

2012-10-31 | GSE29117 | GEO

Mammary carcinomas in WAP-SV40 transgenic mice [gene expression]

Project description:Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates 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 mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis. Gene expression analysis of 25 mammary carcinoma samples of two different WAP-SV40 mouse lines, T1 and NP8. Three involuted mammary gland tissues were included in the study as reference samples.

2012-10-31 | E-GEOD-29117 | biostudies-arrayexpress

Involuted normal mammary gland in WAP-SV40 transgenic mice [gene expression]

2012-10-31 | GSE33038 | GEO

Involuted normal mammary gland in WAP-SV40 transgenic mice [gene expression]

Project description:Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates 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 mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis. Gene expression analysis of 6 involuted normal mammary gland 30 days post weaning in WAP-SV40 T1 and BALB/c samples.

2012-10-31 | E-GEOD-33038 | biostudies-arrayexpress

Mammary carcinomas in WAP-SV40 transgenic mice

Project description:This SuperSeries is composed of the following subset Series: GSE29117: Mammary carcinomas in WAP-SV40 transgenic mice [gene expression] GSE31097: Mammary carcinomas in WAP-SV40 transgenic mice [aCGH] GSE33038: Involuted normal mammary gland in WAP-SV40 transgenic mice [gene expression] Refer to individual Series

2012-10-31 | E-GEOD-31212 | biostudies-arrayexpress

Transcription profiling of mouse WAP-SVT/t transgenic animals during breast cancer formation

Project description:Microarray studies revealed that as a first hit, SV40 T/t-antigen causes deregulation of 462 genes in mammary gland cells (ME-cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell-proliferation specific and Rb-E2F dependent, causing ME-cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells, a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture, breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal-ME-cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal-ME-cells. The profile of retransformants shows that only 38 deregulated genes appear to be tumor-relevant and that none of them is considered to be a typical breast cancer gene. Experiment Overall Design: We have analyzed nine mammary gland tissue segments from three normal NMRI, three WAP-SVT/t mice on the first day of lactation and from three WAP-SVT/t breast cancers (583-tumor 1, 585-tumor 2, 597-tumor 3) as well as three distinct breast cancer derived cell lines (ME-A cells, revertant-ME-B cells and ME-B-T/t cells).

2009-04-25 | E-GEOD-6246 | biostudies-arrayexpress

Global analysis of gene expression in REF52 cells expressing SV40 T antigens

Project description:SV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examine global gene expression in SV40-transformed REF52 cells. SV40 transformation alters the expression of approximately 480 cellular genes. Much of this regulation is consistent with T antigen action on the Rb-E2F pathway.

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