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

Xing, X; Wang, S C; Xia, W; Zou, Y; Shao, R; Kwong, K Y; Yu, Z; Zhang, S et al. · Nat Med · 2000

basic_science · Level V

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Abstract

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter 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 provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

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