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Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro

Oncogene volume 26, pages 4961–4968 (2007)Cite this article

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.

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Acknowledgements

We thank Dr Didier Trono (University of Geneva, Switzerland) for his generous gift of lentiviral vectors LV-THM and LV-tTR/KRAB-Red as well as plasmids pMD2.g, pMDLg/pRRE and pRSV Rev. We are most grateful to our colleague, Martina Vaskova, for her outstanding administrative, technical, and intellectual assistance. We also thank Ahmet Dirim Arslan for technical assistance. Finally, we thank the GOG tumor bank for the EOC TMA. This work was supported by the GOG (a subcontract to WTB), the National Cancer Institute (WTB), and the University of Illinois at Chicago. It was conducted in a facility constructed with support from the NCRR NIH Grant C06RR15482.

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Authors and Affiliations

  1. Gynecologic Oncology Group (GOG) Core Laboratory in Molecular Pharmacology, University of Illinois at Chicago, Chicago, IL, USA

    X He & W T Beck

  2. Department of Biopharmaceutical Sciences, College of Pharmacy, and Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    X He, S B Lim & W T Beck

  3. Department of Pathology, Rush University Medical Center, Chicago, IL, USA

    M Pool & J S Coon

  4. GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA

    K M Darcy

  5. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada

    N Auersperg

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  1. X He
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  2. M Pool
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Correspondence to W T Beck.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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He, X., Pool, M., Darcy, K. et al. Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene 26, 4961–4968 (2007). https://doi.org/10.1038/sj.onc.1210307

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