K-ras mutation promotes colorectal carcinogenesis through GST-π

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We investigated the role of GST-πin growth promotion and apoptosis resistance of colorectal cancer. When a mutated K-ras gene was transfected into K-ras wild colon cancer cell line, GST-πexpression was induced. The transfectant cells showed enhanced growth promotion activity via RAF/MEK/ERK activation and apoptosis resistance by inhibited JNK and p53 pathway. In contrast, GST-πknockdown cells showed growth inhibition and apoptosis enhancement by the inverse action mechanisms. Immunoprecipitation revealed that GST-πwas directly interacted with RAF and JNK respectively. These results indicate that GST-π promote cell growth via direct binding to RAF and subsequent RAF/MEK/ERK activation, and inhibit apoptosis via direct binding to JNK and subsequent p53 apoptosis pathway.