Protein kinase C (PKC) betaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway.

Protein kinase C betaII promotes colon carcinogenesis. Expression of in the colon of transgenic mice induces hyperproliferation and increased susceptibility to colon cancer. To determine molecular mechanisms by which duanyu1531betaII promotes colon cancer, we established rat intestinal epithelial (RIE) cells stably expressing Here we show that cells acquire an invasive phenotype that is blocked by the inhibitor LY379196. Invasion is not observed in RIE cells expressing a kinase-deficient indicating that duanyu1531betaII activity is required for the invasive phenotype. duanyu1531betaII induces activation of K-Ras and the Ras effector, Rac1, in RIE/duanyu1531betaII cells. invasion is blocked by the Mek inhibitor, U0126, and by expression of either dominant negative Rac1 or kinase-deficient atypical Expression of constitutively active Rac1 induces Mek activation and invasion in RIE cells, indicating that Rac1 is the critical downstream effector of duanyu1531betaII-mediated invasion. Taken together, our results define a novel duanyu1531betaII --> Ras --> /Rac1 --> Mek signaling pathway that induces invasion in intestinal epithelial cells. This pathway provides a plausible mechanism by which duanyu1531betaII promotes colon carcinogenesis.

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