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Involvement of cGMP‐dependent protein kinase in colon cancer cells: analysis of cell proliferation, apoptosis and beta‐catenin expression
Author(s) -
Sellak Hassan,
Wu Songwei,
Lincoln Thomas M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.819.5
Subject(s) - cell growth , oncogene , transfection , apoptosis , microbiology and biotechnology , cell cycle , cancer cell , biology , cancer research , cell , protein kinase a , cgmp dependent protein kinase , cell culture , chemistry , kinase , cancer , cyclin dependent kinase 2 , biochemistry , genetics
Cyclic GMP‐dependent protein kinase (PKG) contributes to cell proliferation and differentiation as well as gene regulation. PKG expression is often reduced in cancer cell lines and its role in cell transformation is unknown. In this study, the effects of PKG‐Iß overexpression in cancer cell lines on proliferation, migration and the expression of a proto‐oncogene marker (beta‐catenin) was examined. PKG‐Iß expression in colonic cancer cells, Caco‐1 and Lovo‐1, was performed through stable transfection or lentiviral infection. Cells overexpressing PKG‐Iß proliferate at a higher rate compared to control cells harboring only empty vector, as analyzed by [ 3 H]thymidine incorporation. Incubation with 8‐pCPT‐cGMP (10 μM) increased proliferation of PKG‐Iß‐overexpressing cells compared to the control. Overexpression of PKG‐Iß also had increased levels of apoptosis markers such as caspase 7 and caspase 9 compared to non‐transfected or non‐infected cells. Expression of beta‐catenin, a proto‐oncogene marker, was also analyzed in cells overexpressing PKG‐Iß. The results show that beta‐catenin expression was increased in PKG‐Iß‐overexpressing cells in both cytosolic and nuclear compartments compared to control cells. Taken together, these results suggest that PKG‐Iß may be involved in stimulating apoptosis of colon cancer lines but has no inhibitory effect on cell proliferation. PKG‐Iß may also regulate cell migration by altering the level of beta‐catenin.