Premium
Expression of cyclic guanosine monophosphate‐dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis
Author(s) -
Kwon InKiu,
Schoenlein Patricia V.,
Delk Jennifer,
Liu Kebin,
Thangaraju Muthusmy,
Dulin Nickolai O.,
Ganapathy Vadivel,
Berger Franklin G.,
Browning Darren D.
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23334
Subject(s) - cyclic guanosine monophosphate , angiogenesis , cancer research , medicine , protein kinase a , colorectal cancer , cgmp dependent protein kinase , cd31 , carcinogenesis , cancer cell , cancer , apoptosis , kinase , endocrinology , biology , cell cycle , microbiology and biotechnology , cyclin dependent kinase 2 , nitric oxide , biochemistry
BACKGROUND Type 1 cyclic guanosine monophosphate (cGMP)‐dependent protein kinase (PKG) reportedly has exhibited antitumor properties, and its expression is down‐regulated in many tumors. METHODS The authors recently demonstrated that PKG re‐expression in metastatic colon carcinoma cells results in decreased tumorigenesis: In the current study, they addressed that mechanism. RESULTS Over‐expression of PKG in SW620 cells produced smaller, more apoptotic subcutaneous tumors in athymic mice, but the observed effect of PKG expression on growth and apoptosis in vitro was minimal. Closer examination of the subcutaneous xenografts revealed highly vascular tumors produced by the parental SW620 cells, which contrasted greatly with the PKG‐expressing tumors, in which cell growth was limited to “islands” surrounding CD31‐positive cells. The idea that PKG expression was associated with reduced tumor angiogenesis was supported by decreased levels of vascular endothelial growth factor in these tumors compared with tumors that were derived from parental SW620 cells. Investigation of potential mechanisms revealed that PKG expression was associated with reduced levels of β‐catenin compared with parental cells. Moreover, this effect of exogenous PKG on β‐catenin expression in SW620 cells also occurred in vitro, where the decrease was associated with reduced T‐cell factor‐dependent transcription. CONCLUSIONS Together the findings indicated that PKG down‐regulation in colon cancer cells is important for optimal tumor angiogenesis and that regulation of β‐catenin expression may be important to this process. Cancer 2008. © 2008 American Cancer Society.