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CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential

Oncogene volume 21, pages 4435–4447 (2002)Cite this article

Abstract

Although early stage ovarian cancer can be effectively treated with surgery and chemotherapy, the majority of cases present with advanced disease, which remains essentially incurable. Unfortunately, little is known about the genes important for the development and progression of this disease. In this study, the expression of 68 phosphatases was determined in immortalized ovarian epithelial cells (IOSE) and compared to ovarian cancer cell lines. CL100, a dual specificity phosphatase, displayed 10–25-fold higher expression in normal compared to malignant ovarian cell lines. Immunohistochemical staining of normal ovaries and 68 ovarian cancer specimens confirmed this differential expression. Re-expression of CL100 in ovarian cancer cells decreased adherent and non-adherent cell growth and induced phenotypic changes including loss of filopodia and lamellipodia with an associated decrease in cell motility. Induced expression of CL100 in ovarian cancer cells suppressed intraperitoneal tumor growth in nude mice. These results show for the first time that CL100 expression is altered in human ovarian cancer, that CL100 expression changes cell morphology and motility, and that it suppresses intraperitoneal growth of human ovarian epithelial cancer. These data suggest that down-regulation of CL100 may play a role in the progression of human ovarian cancer.

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Acknowledgements

The ovarian cell lines used in this study were obtained as generous gifts from Dr Scott Rose (University of California, San Diego, CA, USA), Dr David Spriggs (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Dr Jacques DeGreve (AZ-VUB-Oncologisch Centrum, Brussels, Belgium), and Dr Louis Dubeau (Norris Cancer Center, University of California, Los Angeles). The human cyclin D1 promoter plasmids were derived from fragments provided by Dr A Arnold and Dr R Pestell and constructed by Dr Osami Tetsu with Dr Frank McCormick. Protein lysates from HOSE cells were a kind gift of Dr Mok (Harvard University, Boston, MA, USA). We thank these individuals for their generous gifts. We thank Aaron Bell for his expert technical assistance. This work was supported in part by grants DK52825, CA88906 and DAMD-99-17-9426 to P Dent.

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Author notes

  1. Luis M Montuenga & Silvestre Vicent

    Present address: Cytology and Histology Department, University of Navarra, Pamplona, Spain

Authors and Affiliations

  1. Cell and Cancer Biology Department, National Cancer Institute, 9610 Medical Center Drive, Rockville, 20850, Maryland, MD, USA

    Ramon G Manzano, Luis M Montuenga, Ichiro Kinoshita, Silvestre Vicent, Ginger J Gardner, PhuongMai Nguyen, Yung-Hyun Choi, Jane Trepel & Michael J Birrer

  2. Department of Medicine, Louisiana State University Medical Center, Shreveport, 71130-3932, Louisiana, LA, USA

    Mark Dayton

  3. Department of Radiation Oncology, Massey Cancer Center, Medical College of Virginia, Virginia Commonwealth University, 23298, Richmond, Virginia, VA, USA

    Paul Dent

  4. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, V6H 3V5, British Columbia, Canada

    Nelly Auersperg

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Correspondence to Michael J Birrer.

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Manzano, R., Montuenga, L., Dayton, M. et al. CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential. Oncogene 21, 4435–4447 (2002). https://doi.org/10.1038/sj.onc.1205542

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