Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis

In Kiu Kwon, Patricia V Schoenlein, Jennifer Delk, Kebin Liu, Muthusamy Thangaraju, Nickolai O. Dulin, Vadivel Ganapathy, Franklin G. Berger, Darren D Browning

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1462-1470
Number of pages9
JournalCancer
Volume112
Issue number7
DOIs
StatePublished - Apr 1 2008

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Colon
Carcinoma
Catenins
Neoplasms
TCF Transcription Factors
Growth
Islands
Heterografts
Nude Mice
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Blood Vessels
Carcinogenesis
Down-Regulation
Apoptosis

Keywords

  • β-catenin
  • Angiogenesis
  • Apoptosis
  • Cancer
  • Cyclic guanosine monophosphate
  • Protein kinase
  • Xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis. / Kwon, In Kiu; Schoenlein, Patricia V; Delk, Jennifer; Liu, Kebin; Thangaraju, Muthusamy; Dulin, Nickolai O.; Ganapathy, Vadivel; Berger, Franklin G.; Browning, Darren D.

In: Cancer, Vol. 112, No. 7, 01.04.2008, p. 1462-1470.

Research output: Contribution to journalArticle

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AU - Schoenlein, Patricia V

AU - Delk, Jennifer

AU - Liu, Kebin

AU - Thangaraju, Muthusamy

AU - Dulin, Nickolai O.

AU - Ganapathy, Vadivel

AU - Berger, Franklin G.

AU - Browning, Darren D

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N2 - 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.

AB - 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.

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