Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms. | ||||||||
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A role for cyclic-GMP dependent protein kinase in anoikis.Hou Y, Wong E, Martin J, Schoenlein PV, Dostmann WR, Browning DD Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30809, USA. Anoikis is an essential process in which a loss of adhesion to the substratum alters intracellular signaling pathways that lead to apoptosis. Using phosphorylation of vasodilator stimulated phosphoprotein (VASP) as an indicator of cGMP-dependent protein kinase (PKG) activity in vivo, it was found that suspension of the colon epithelial cell line (CCD841) leads to rapid and transient activation of PKG that lasted several hours. The colon carcinoma lines SW480 and SW620 do not express endogenous PKG, but exogenously expressed PKG was similarly activated upon cell suspension. To determine whether PKG has a role in apoptosis following cell suspension, poly-ADP ribose polymerase (PARP) cleavage and propidium iodide staining were measured. After 24 h in suspension it was found that approximately 50% of CCD841 cells exhibited apoptosis, whereas apoptosis was not detected in either of the colon carcinoma cell lines. Inhibition of type 1 PKG by expression of a dominant negative PKG construct (G1alphaR-GFP), or by incubation with the PKG inhibitor peptide DT-2, blocked apoptosis in suspended CCD841 cells by approximately 50%. Furthermore, expression of exogenous PKG in SW620 and SW480 cells conferred partial sensitivity anoikis. Taken together these findings indicate that PKG has an important role in the induction of apoptosis following suspension of normal colon epithelial cells, and loss of PKG expression in colon tumor cells may contribute to resistance to anoikis. Published 13 February 2006 in Cell Signal, 18(6): 882-8.
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