Transcriptomics,Genomics

Dataset Information

32

Gene expression profiling of mammary epithelial cells from mice transiently exposed to tamoxifen


ABSTRACT: 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. Overall design: Two experimental groups: Tamoxifen-treated group and control group. We used triplicate pools of mammary glands from control or tamoxifen-treated mice (5 mice per pool) for preparation of MEC’s total RNA isolation followed by Affymetrix array profiling using Affymetrix GeneChip Mouse Exon 1.0 ST array.

INSTRUMENT(S): [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version]

SUBMITTER: Chad Creighton  

PROVIDER: GSE77948 | GEO | 2018-04-17

REPOSITORIES: GEO

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Publications

Reprogramming of the estrogen responsive transcriptome contributes to tamoxifen-dependent protection against tumorigenesis in the p53 null mammary epithelial cells.

Palaniappan Murugesan M   Edwards David D   Creighton Chad J CJ   Medina Daniel D   Conneely Orla M OM  

PloS one 20180328 3


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. Transient exposure of p53 null mice to the anti-estrogen, tamoxifen leads to sustained and robust  ...[more]

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