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Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer

Oncogene volume 30, pages 356–365 (2011)Cite this article

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Abstract

Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were upregulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays, one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC, whereas there were more all-positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the majority of cases were stained all positive for both PTB and SRp20, and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC.

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Acknowledgements

We thank the Gynecologic Oncology Group (GOG) Tissue Bank for providing unstained ovarian tumor TMAs. We thank our colleague, Martina Vaskova, for her outstanding administrative assistance. We also thank Dr Richard Gemeinhart for allowing us to use his IX70 microscope and Ernest Gemeinhart for his excellent technical assistance with microscopy. This work was supported by the National Cancer Institute Grants CA40570 and CA138762 to WTB, CA27469 to the GOG, GOG Tissue Bank and GOG Molecular Pharmacology Core Lab and CA37517 to the GOG Statistical and Data Center as well as the Ovarian Cancer Research Fund (XH), Rush University Medical Center 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. Department of Biopharmaceutical Sciences, College of Pharmacy and Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    X He, A D Arslan, T-T Ho & W T Beck

  2. Gynecologic Oncology Group (GOG) Core Laboratory for Molecular Pharmacology, College of Pharmacy and Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    X He & W T Beck

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

    M D Pool & J S Coon

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

    K M Darcy

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He, X., Arslan, A., Pool, M. et al. Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer. Oncogene 30, 356–365 (2011). https://doi.org/10.1038/onc.2010.426

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