Negative Regulation of Tumor Suppressor p53 Transcription in Breast Cancer Cells
Abstract
Recently, there is emerging information to link STAT3 signaling pathway with tumor suppressor p53. Our previous studies have demonstrated that the transcription of the p53 gene in breast cancer cells was down regulated by cytokine oncostatin M (OM). The second goal of our proposal was to evaluate the critical role of STAT3 in OM-mediated regulation of p53 transcription. In this report, we show that blocking STAT3 transactivating activity by the expression of a dominant negative mutant of STAT3 (dnStat3) reversed the OM inhibitory effects on p53 promoter activity and p53 protein expression, demonstrating an involvement of STAT3 in OM-mediated negative regulation of the p53 transcription. In addition, to determine functional roles p53 in the process of proliferation and differentiation of breast cancer cells, we generated stable cell lines (MCF-7 ptsp53) that express p53Val135 temperature-sensitive mutant. When cultured at 37 deg C, p53Val135 transfectants expressed exogenous p53 in a mutant conformation that acted as a dominant negative mutant and inhibited the transactivation of endogenous p53. In contrast, at permissive temperature 32 deg C, the p53Val135 mutant resumed normal conformation and behaved as the wild-type p53. We found that overexpression of functional p53 in MCF-7 cells leads to growth arrest at the G2/M phase of the cell cycle without an induction of apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408185
Entities
People
- Jingwen Liu
Organizations
- Palo Alto Veterans Institute for Research