Project description:The aim of our work was the comparison of human and mouse gene expression data and to identify a conserved breast tumor gene set. The results encourage the usefulness of transgenic mice as a model for human breast cancer formation and therapy. Experiment Overall Design: The aim of our work was to establish a database for breast cancer gene expression data in order to compare human and mouse breast cancer. We identified human and mouse homologues genes and compared the expression profile of 24 human breast tumors with six WAP-SVT/t breast tumors (WAP-SVT/t animals, line 8). Our studies confirmed the heterogeneity in gene expression of human as well as mouse breast cancer cells. However, 63 genes were found to be differentially expressed (upregulated: 40; downregulated: 23 genes) in at least 75% of the breast tumors of both species.
Project description:The aim of our work was the comparison of human and mouse gene expression data and to identify a conserved breast tumor gene set. The results encourage the usefulness of transgenic mice as a model for human breast cancer formation and therapy. Keywords: Comparison of gene expression data The aim of our work was to establish a database for breast cancer gene expression data in order to compare human and mouse breast cancer. We identified human and mouse homologues genes and compared the expression profile of 24 human breast tumors with six WAP-SVT/t breast tumors (WAP-SVT/t animals, line 8). Our studies confirmed the heterogeneity in gene expression of human as well as mouse breast cancer cells. However, 63 genes were found to be differentially expressed (upregulated: 40; downregulated: 23 genes) in at least 75% of the breast tumors of both species.
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).
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. Keywords: Tumorigenesis, Breast cancer, SV40 T/t antigen
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.
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.