Epigenetic Control of Prostate Cancer Metastasis: Role of Runx2 Phosphorylation.

摘要

The goal of this project is to determine the role of ERKIMAP kinase phosphorylation of the RUNX2 transcription factor in the metastasis of prostate cancer cells. Major accomplishments were: a. Demonstration that Runx2 must be phosphorylated at Ser 301 and Ser 319 to stimulate prostate cancer cell gene expression, in vitro cell migration and invasion as well as in vivo tumor growth. b. Demonstration that anti-Runx2-S319-P antibody is able to specifically stain human prostate tumor samples on tissue microarrays without staining normal prostate tissue or non-cancerous prostate sample (e.g. benign prostate hyperplasia). In addition, this antibody was able to discriminate between invasive, high Gleason score tumors and non-metastatic tumors These results support our overall hypothesis that RUNX2 phosphorylation is a critical determinant of prostate tumor formation/growth and metastasis and that P-Runx2 is a cancer biomarker and potential therapeutic target.