PARP regulates TGF-β receptor type II expression in estrogen receptor-positive breast cancer cell lines

Background: Expression of the tumor suppressor gene, transforming growth factor beta receptor type II (T beta RII) is often reduced in estrogen receptor-positive breast cancer cells leading to uninhibited tumor cell growth. A clear understanding of its regulation is necessary to identify potential mechanisms to re-express this tumor suppressor gene. Materials and Methods: The regulation of T beta RII expression was studied by utilizing 5' promoter deletion constructs, followed by EMSA analyses. The resulting binding protein was affinity purified and identified by mass spectrophotometry. Results: An inverted CCAAT box centered at -79 was found to be essential for T beta RII promoter activity. Purification of the protein binding to this region and subsequent mass spectrophotometric analysis identified the binding protein as poly(ADP-ribose)polyinerase I (PARP). ChIP assays verified that PARP interacted with the TPRII promoter in vivo. Conclusion: The present study demonstrated that PARP is important for T beta RII expression in estrogen receptor-positive breast cancer cell lines.