<i>PCOTH</i>, a Novel Gene Overexpressed in Prostate Cancers, Promotes Prostate Cancer Cell Growth through Phosphorylation of Oncoprotein TAF-Iβ/SET

DOI PDF 被引用文献3件
  • Yoshio Anazawa
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Hidewaki Nakagawa
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Mutsuo Furihara
    2Tumor Pathology and
  • Shingo Ashida
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Kenji Tamura
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Hiroki Yoshioka
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Taro Shuin
    3Urology, Kochi Medical School, Nankoku; and
  • Tomoaki Fujioka
    4Department of Urology, Iwate Medical University, Morioka, Japan
  • Toyomasa Katagiri
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of
  • Yusuke Nakamura
    1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Departments of

抄録

<jats:title>Abstract</jats:title> <jats:p>Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Iβ/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Iβ expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Iβ pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 65 (11), 4578-4586, 2005-06-01

    American Association for Cancer Research (AACR)

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