title: CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential.
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.
authors.affiliation: Cell and Cancer Biology Department, National Cancer Institute, 9610 Medical Center Drive, Rockville, Maryland 20850, USA.
authors.forename: Ramon G
authors.initials: RG
authors.lastname: Manzano
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montuenga
authors.forename: Mark
authors.initials: M
authors.lastname: Dayton
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Silvestre
authors.initials: S
authors.lastname: Vicent
authors.forename: Ginger J
authors.initials: GJ
authors.lastname: Gardner
authors.forename: PhuongMai
authors.initials: P
authors.lastname: Nguyen
authors.forename: Yung-Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Jane
authors.initials: J
authors.lastname: Trepel
authors.forename: Nelly
authors.initials: N
authors.lastname: Auersperg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D054638:Dual Specificity Phosphatase 1; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D017874:Immediate-Early Proteins; D019938:Cyclin D1; D012313:RNA; D008156:Luciferases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D010744:Phosphoric Monoester Hydrolases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases