Original Article
Oncogene (2007) 26, 4961–4968; doi:10.1038/sj.onc.1210307; published online 19 February 2007
Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro
X He1,2, M Pool3, K M Darcy4, S B Lim2, N Auersperg5, J S Coon3 and W T Beck1,2
- 1Gynecologic Oncology Group (GOG) Core Laboratory in Molecular Pharmacology, University of Illinois at Chicago, Chicago, IL, USA
- 2Department of Biopharmaceutical Sciences, College of Pharmacy, and Cancer Center, University of Illinois at Chicago, Chicago, IL, USA
- 3Department of Pathology, Rush University Medical Center, Chicago, IL, USA
- 4GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA
- 5Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
Correspondence: Dr WT Beck, Department of Biopharmaceutical Sciences (MC865), 833 South Wood Street, University of Illinois at Chicago, Chicago, IL 60612, USA. E-mail: WTBeck@uic.edu
Received 28 July 2006; Revised 26 December 2006; Accepted 1 January 2007; Published online 19 February 2007.
Abstract
Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and in vitro invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.
Keywords:
epithelial ovarian cancer, polypyrimidine tract-binding protein, RNA interference, tissue microarray, tumorigenesis
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