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  • Title: Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early event during premalignant colonic epithelial hyperproliferation.
    Author: Kunte DP, Wali RK, Koetsier JL, Hart J, Kostjukova MN, Kilimnik AY, Pyatkin IG, Strelnikova SR, Roy HK.
    Journal: FEBS Lett; 2005 Jul 04; 579(17):3497-502. PubMed ID: 15961079.
    Abstract:
    Hyperproliferation of the premalignant epithelium is critical for colonic carcinogenesis; however the mechanisms remain largely unexplored. We report herein that prior to occurrence of neoplastic lesions in the azoxymethane-rat model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase (Csk) was down-regulated with a concomitant increase in Src activity. Furthermore, pharmacological or genetic (RNA interference) inhibition of Csk resulted in increased proliferation in colon cancer cell lines through the mitogen-activated protein kinase dependent pathway. Thus, we demonstrate, for the first time, that Csk suppression is an important early event in colorectal cancer pathogenesis.
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