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.
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.
Authors: I-K Kwon; R Wang; M Thangaraju; H Shuang; K Liu; R Dashwood; N Dulin; V Ganapathy; D D Browning Journal: Oncogene Date: 2010-03-29 Impact factor: 9.867
Authors: Jason D Whitt; Nan Li; Heather N Tinsley; Xi Chen; Wei Zhang; Yonghe Li; Bernard D Gary; Adam B Keeton; Yaguang Xi; Ashraf H Abadi; William E Grizzle; Gary A Piazza Journal: Cancer Prev Res (Phila) Date: 2012-05-03
Authors: Bianca N Islam; Sarah K Sharman; Yali Hou; Allison E Bridges; Nagendra Singh; Sangmi Kim; Ravindra Kolhe; Jimena Trillo-Tinoco; Paulo C Rodriguez; Franklin G Berger; Subbaramiah Sridhar; Darren D Browning Journal: Cancer Prev Res (Phila) Date: 2017-05-03
Authors: Graciele Almeida de Oliveira; Robert Y S Cheng; Lisa A Ridnour; Debashree Basudhar; Veena Somasundaram; Daniel W McVicar; Hugo Pequeno Monteiro; David A Wink Journal: Antioxid Redox Signal Date: 2016-10-31 Impact factor: 8.401
Authors: John C Flickinger; Jeffrey A Rappaport; Joshua R Barton; Trevor R Baybutt; Amanda M Pattison; Adam E Snook; Scott A Waldman Journal: Biomark Med Date: 2021-01-20 Impact factor: 2.851