PARP Regulates TGF-β Receptor Type II Expression in Estrogen Receptor-positive Breast Cancer Cell Lines

Abstract

Background: Expression of the tumor suppressor gene, transforming growth factor beta receptor type II (TβRII) 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 TβRII 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 TβRII 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 TβRII promoter in vivo. Conclusion: The present study demonstrated that PARP is important for TβRII expression in estrogen receptor-positive breast cancer cell lines.