Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis.
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 beta-catenin compared with parental cells. Moreover, this effect of exogenous PKG on beta-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 beta-catenin expression may be important to this process.
Kwon
In-Kiu
IK
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Schoenlein
Patricia V
PV
Delk
Jennifer
J
Liu
Kebin
K
Thangaraju
Muthusmy
M
Dulin
Nickolai O
NO
Ganapathy
Vadivel
V
Berger
Franklin G
FG
Browning
Darren D
DD
D000230:Adenocarcinoma / Q000098:blood supply* / Q000201:enzymology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000201:enzymology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C467480:vascular endothelial growth factor A, mouse; D017869:Cyclic GMP-Dependent Protein Kinases