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.


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.


CONCLUSIONS
The present study demonstrated that PARP is important for TbetaRII expression in estrogen receptor-positive breast cancer cell lines.
Sterling
Julie A
JA
Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA. sterlingj@uthscsa.edu
Wu
Liang
L
Banerji
Sunandita S
SS
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D023081:CCAAT-Binding Factor; D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II