Expression profiling of the mouse prostate after castration and hormone replacement: implication of H-cadherin in prostate tumorigenesis

Authors

  • Xi-De Wang,

    1. Department of Molecular Biology, MS 72, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, U.S.A.
      Tel: +1 650 225 8101
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    • *Present address: Bristol-Myers Squibb, P.O. Box 5400, Princeton, NJ 08543, U.S.A.

  • Bu-Er Wang,

    1. Department of Molecular Biology, MS 72, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, U.S.A.
      Tel: +1 650 225 8101
      Fax: +1 650 225 6240
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  • Robert Soriano,

    1. Department of Molecular Biology, MS 72, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, U.S.A.
      Tel: +1 650 225 8101
      Fax: +1 650 225 6240
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  • Jiping Zha,

    1. Department of Pathology, Genentech Inc., South San Francisco, CA 94080, U.S.A.
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  • Zemin Zhang,

    1. Department of Bioinformatics, Genentech Inc., South San Francisco, CA 94080, U.S.A.
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  • Zora Modrusan,

    1. Department of Molecular Biology, MS 72, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, U.S.A.
      Tel: +1 650 225 8101
      Fax: +1 650 225 6240
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  • Gerald R. Cunha,

    1. Department of Anatomy and Urology, University of California at San Francisco, San Francisco, CA 94143, U.S.A.
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  • Wei-Qiang Gao

    Corresponding author
    1. Department of Molecular Biology, MS 72, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, U.S.A.
      Tel: +1 650 225 8101
      Fax: +1 650 225 6240
      ✉ E-mail: gao@gene.com
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✉ E-mail: gao@gene.com

Abstract

Abstract Mice have been used extensively for studying normal prostate development and for generation of transgenic or knock-out prostate cancer animal models. To understand systematically and thoroughly the androgen responsive program in the mouse prostate, we carried out microarray analysis to profile gene expression changes during prostate involution and re-growth triggered by castration and subsequent hormone replacement. Genes with significant changes in these two processes were identified and gene ontology analyses revealed that they were mainly involved in response mechanisms, cell adhesion, metabolism, protein metabolism, and cell-cycle progression. The changes observed during prostate involution were largely reversed during re-growth. Sixty-four genes, including Nkx3.1 and probasin, and 65 other genes, including insulin-like growth factor binding protein 3 and H-cadherin (H-Cad), were further identified respectively as androgen-responsive genes and genes inversely correlated with androgen, based on their down- or up-regulation following castration and up- or down-regulation following androgen replacement. Potential androgen-responsive elements were found in the 5′ upstream promoter region of 47 of those 65 genes, suggesting a potential suppression mechanism by androgen receptor. Of these, the role of H-Cad in tumorigenesis was further evaluated. Reduction of H-Cad transcript level was found in the majority of human prostate cancer cell lines and prostatic adenocarcinoma samples examined. Furthermore, induced H-Cad expression in DU145 cells, and knock-down of H-Cad expression in BPH1 cells inhibited and facilitated tumorigenicity, respectively. Taken together, our study provides a molecular understanding of the mouse prostate involution and re-growth processes and identifies a set of genes that are inversely correlated with androgen and may be potentially suppressive for tumorigenesis.

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