The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis

Because HER-2/neu overexpression is important in cancer development, we loo ked for a method of suppressing the cell transformation mediated by HER-2/n eu overexpression. We have identified that the DNA-binding protein PEA3, wh ich is encoded by a previously isolated gene of the ets family, specificall y targeted a DNA sequence on the HER-2/neu promoter and downregulated the p romoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells . This is a new approach to targeting HER-2/neu overexpression and also pro vides a rationale to the design for repressors of diseases caused by overex pression of pathogenic genes.