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Down‐regulation of the tumor suppressor gene C‐terminal Src kinase: An early event during premalignant colonic epithelial hyperproliferation
Author(s) -
Kunte Dhananjay P.,
Wali Ramesh K.,
Koetsier Jennifer L.,
Hart John,
Kostjukova Maria N.,
Kilimnik Anna Y.,
Pyatkin Ilia G.,
Strelnikova Svetlana R.,
Roy Hemant K.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.030
Subject(s) - azoxymethane , carcinogenesis , proto oncogene tyrosine protein kinase src , cancer research , colorectal cancer , kinase , biology , tumor suppressor gene , cancer , suppressor , microbiology and biotechnology , genetics
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.