Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of PTEN-deficiency in luminal MMTV-ErbB-2 mouse model to investigate its effect on mammary tumorigenesis and metastasis

ABSTRACT: Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways. Experiment Overall Design: Common reference design. 9 samples (including 2 normal tissue and 7 tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Robert Lesurf

PROVIDER: E-GEOD-13916 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PTEN deficiency in a luminal ErbB-2 mouse model results in dramatic acceleration of mammary tumorigenesis and metastasis.

Schade Babette B Rao Trisha T Dourdin Nathalie N Lesurf Robert R Hallett Michael M Cardiff Robert D RD Muller William J WJ

The Journal of biological chemistry 20090512 28

Overexpression and/or amplification of the ErbB-2 oncogene as well as inactivation of the PTEN tumor suppressor are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the murine mammary tumor virus (MMTV) promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (M ...[more]

PMID: 19435886

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Dataset Information

Transcription profiling of PTEN-deficiency in luminal MMTV-ErbB-2 mouse model to investigate its effect on mammary tumorigenesis and metastasis

Publications

PTEN deficiency in a luminal ErbB-2 mouse model results in dramatic acceleration of mammary tumorigenesis and metastasis.

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