Abstract 2853 PRMT7 Negatively Regulates the Expression p53 in Response to DNA Damage

Protein Arginine Methyltransferase 7 (PRMT7) is the only member of the protein arginine methyltransferase protein family that monomethylates its protein substrates. PRMT7 is found in both the nucleus and cytoplasm of breast cells and is believed to play a robust role in the tumorigenesis and metastasis of breast cancer. The goal of this project is to uncover possible pathways for PRMT7 to promote cancer progression. A preliminary antibody array was performed to determine the regulation of known cancer-related proteins by PRMT7. An early-stage human breast cancer cell line, MCF-7, was transfected with plasmid pCDH1-hPRMT7-GFP to over-express PRMT7. Qualitative and quantitative analysis of detectable expression changes compared to sham transfection revealed a decrease in p53 expression, a protein not previously associated with PRMT7. Upon DNA damage, p53 can induce the expression of genes like p21, which inhibit cyclin-dependent kinases (CDKs) and halt the cell cycle. This pause allows the cell time to repair the DNA damage before proceeding with division. Our current research aims at identifying the mechanisms of action by which PRMT7 regulates p53. For example, PRMT7 may monomethylate proteins directly implicated in the expression or activity of p53. Successful completion of this project will provide novel insights into how PRMT7 contributes to breast cancer progression.