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Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early event during premalignant colonic epithelial hyperproliferation.

Kunte DP, Wali RK, Koetsier JL, Hart J, Kostjukova MN, Kilimnik AY, Pyatkin IG, Strelnikova SR, Roy HK

Department of Internal Medicine, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, USA.

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.

Published 1 July 2005 in FEBS Lett, 579(17): 3497-502.
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Colorectal Cancer Research Today Archive:

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Colorectal Cancer Books

The Intelligent Patient Guide to Colorectal Cancer: Information, risk, prevention, symptoms, signs, diagnosis, stage, surgery, radiation, chemotherapy, prognosis, treatment of/for colon rectal cancer.

The Intelligent Patient Guide to Colorectal Cancer: Information, risk, prevention, symptoms, signs, diagnosis, stage, surgery, radiation, chemotherapy, prognosis, treatment of/for colon rectal cancer.