PARP regulates TGF-beta 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 (TbetaRII) 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 TbetaRII 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 TbetaRII promoter activity. Purification of the protein binding to this region and subsequent mass spectrophotometric analysis identified the binding protein as poly(ADP-ribose)polymerase I (PARP). ChIP assays verified that PARP interacted with the TbetaRII promoter in vivo. CONCLUSION The present study demonstrated that PARP is important for TbetaRII expression in estrogen receptor-positive breast cancer cell lines.