BF Holds the J. Harold and Edna L. LaBriola Chair in Genetic Orthopedic Research at USC.
Original Research Article
Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation†
Article first published online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 2276–2282, May 2012
How to Cite
Baniwal, S. K., Little, G. H., Chimge, N.-O. and Frenkel, B. (2012), Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation. J. Cell. Physiol., 227: 2276–2282. doi: 10.1002/jcp.22966
Conflict of interest: None
- Issue published online: 23 JAN 2012
- Article first published online: 23 JAN 2012
- Accepted manuscript online: 1 AUG 2011 08:41AM EST
- Manuscript Accepted: 25 JUL 2011
- Manuscript Received: 20 JUL 2011
- National Institute of Health RO1 and NCRR grants. Grant Numbers: DK071122 DK071122S1, CA 109147, AR047052, and SC CTSI UL1 RR03986
Prolactin-Induced Protein (PIP) is a small polypeptide expressed by breast and prostate cancer (BCa, PCa) cells. However, both the regulation of PIP expression and its function in cancer cells are poorly understood. Using BCa and PCa cells, we found that Runx2, a pro-metastatic transcription factor, functionally interacts with the Androgen Receptor (AR) to regulate PIP expression. Runx2 expression in C4-2B PCa cells synergized with AR to promote PIP expression, whereas its knockdown in T47D BCa cells abrogated basal as well as hormone stimulated PIP expression. Chromatin immunoprecipitation (ChIP) assays showed that Runx2 and AR co-occupied an enhancer element located ∼11 kb upstream of the PIP open reading frame, and that Runx2 facilitated AR recruitment to the enhancer. PIP knockdown in T47D cells compromised DHT-stimulated expression of multiple AR target genes including PSA, FKBP5, FASN, and SGK1. The inhibition of AR activity due to loss of PIP was attributable at least in part to abrogation of its nuclear translocation. PIP knockdown also suppressed T47D cell proliferation driven by either serum growth factors or dihydrotestosterone (DHT). Our data suggest that Runx2 controls a positive feedback loop between androgen signaling and PIP, and pharmacological inhibition of PIP may be useful to treat PIP positive tumors. J. Cell. Physiol. 227: 2276–2282, 2012. © 2011 Wiley Periodicals, Inc.