Development of PEA3 as a Potential Gene Therapy Agent for Breast Cancer
Abstract
HER-2/neu overexpression plays an important role for cancer development. To suppress cell transformation mediated by HER-2/neu overexpression, we identified a DNA- binding protein PEA3 of the Ets gene family which specifically targeted a DNA sequence on the HER2/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. A competition model to elucidate the molecular mechanism for the transcription inhibition of Her-2/neu by PEA3 was proposed. PEA3 directly binds to the HER-2/neu promoter and competition of PEA3 with other Ets transactivating factor(s) for a positive regulatory motif on the Her-2/neu promoter may acount for the downregulation of Her-2/neu transcription by PEA3.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA381107
Entities
People
- Zhenming Yu
Organizations
- The University of Texas MD Anderson Cancer Center