Epigenetic Control of Prostate Cancer Metastasis: Role of Runx2 Phosphorylation
Abstract
The goal of this project is to determine the role of ERK/MAP kinase phosphorylation of the RUNX2 transcription factor in the metastasis of prostate cancer cells. In the first budget year, we achieved the following: a. Generation of lentivirus and adenovirus sectors expressing WT RUNX2 and S301A, S319A phosphorylation-deficient RUNX2. Isolation of stable PC3 and LnCaP cell lines expressing WT and mutant RUNX2. b. Demonstration that phosphorylation-deficient RUNX2 has reduced ability to induce metastasis-associated genes in PCa cells. c. Demonstration that phosphorylation-deficient RUNX2 has reduced ability to stimulate in vitro migration of PC-3 PCa cells. d. Demonstration that phosphorylation-deficient RUNX2 has reduced ability to induce VEGF synthesis and stimulate in vitro angiogenic activity of HDMECs. e. Demonstration that phosphorylation-deficient RUNX2 has reduced ability to stimulate in vitro invasion of PC-3 cells. f. Demonstration that RUNX2-S-319 phosphorylation is dramatically elevated in prostate cancer cells versus benign prostate hyperplasia and that elevated levels of P-RUNX2 persist in more advanced primary tumors and metastases. These results support our overall hypothesis that RUNX2 phosphorylation is a critical determinant of tumorogenicity and metastasis of prostate tumor cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2013
- Accession Number
- ADA580104
Entities
People
- Renny T Franceschi
Organizations
- University of Michigan