Anti-tumor functions of type 1 cGMP-dependent protein kinase Free

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Cyclic-GMP has been found to have anti-tumor properties in colon cancer cells but the importance of type-1 cGMP-dependent protein kinase (PKG) in tumor biology is not known. Studies with a cDNA array revealed that PKG expression was reduced in many tumors compared to respective normal tissue. This decrease in PKG expression was confirmed using quantitative RT-PCR and western blotting of matched colon specimens from normal epithelium and tumor tissue, and also in colon derived cell lines where luciferase reporter analysis revealed that the decrease was at the transcriptional level. Using SW620 colon carcinoma cells engineered for inducible expression, it was found that exogenous PKG1β decreased tumor growth and invasiveness, and completely blocked metastasis in nude mouse xenografts. Further analysis of subcutaneous tumors revealed decreased β-catenin levels in PKG expressing tissues, suggesting the involvement of this pathway downstream of PKG. These studies demonstrate the anti-tumor properties of PKG and highlight the potential of this enzyme as a therapeutic target.