Negative Regulation of Tumor Suppressor p53 Transcription in Breast Cancer Cells
Abstract
The original proposed specific tasks of this Idea grant were threefold: (1) to identify the cis-acting elements and the trans-acting factors that are responsible for the cytokine oncostatin M (OM)-induced suppression of p53 transcription in breast cancer cells, (2) to determine whether ERK and STAT3 play essential roles in OM-mediated suppression of p53 transcription, and (3) to over express p53 in a tetracycline regulated expression system. These 3 tasks have been successfully accomplished. We have identified a novel cis-regulatory element, designated as PE21, that mediates the OM-induced suppression of p53 transcription. By conducting electrophoretic mobility shift assay connected with UV-crosslinking, we have detected a protein of 87 kDa that specifically binds to the PE21 element. We have demonstrated 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, indicating 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 p53Va1135 temperature-sensitive mutant. We found that overexpression of functional p53 in MCF-7 cells leads to growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA431331
Entities
People
- Jingwen Liu
Organizations
- Palo Alto Veterans Institute for Research