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.