Training in support of research entitled "Development of PEA3 as a Potential Gene Therapy Agent for Breast Cancer"

Overexpression and/or amplification of HER-2/neu has been implicated in the genesis of a number of human cancers, especially breast and ovarian cancers. Transcriptional upregulation has been shown to contribute significantly to the overexpression of this gene. PEA3 is a DNA binding transcriptional factor and its consensus sequence exists on the HER-2/neu promoter. We transfected PEA3 into the human breast and ovarian cancer cells that overexpress HER-2/neu and showed that PEA3 dramatically represses HER-2/neu transcription. and suppresses the oncogenic neu-mediated transformation in mouse fibroblasts. Expression of PEA3 selectively blocks the growth of human cancer cells that overexpress HER-2/neu. Studies in the orthotopic ovarian cancer model demonstrated that expression of PEA3 preferentially inhibits growth and tumor development of human cancer cells that overexpress HER-2/neu, through down regulation of HER-2/neu-p185. Thus, PEA3 is a negative regulator of HER-2/neu gene expression and functions as a tumor suppressor gene in the HER-2/neu overexpressing human cancer cells.