title: Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines.
abstract: In light of the poor prognosis for ovarian cancer patients, the research continues for innovative and efficacious treatment modalities. Along with surgical and chemotherapeutic regimens, gene therapy has emerged as one of the leading contenders in the treatment armamentarium. Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. However, the biological function of Hepsin expression remains unclear. Apoptotic cell was increasingly common among higher proportions of Hepsin transfectants. We discovered that first-time stable transfectants of Hepsin significantly inhibited cell growth in the monolayer, anchorage-independent cell growth in the soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines. These results demonstrated that Hepsin has a potential therapeutic effect that inhibits through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Our findings in this study identify Hepsin as a target for new approaches in ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. k-nakamu@cc.okayama-u.ac.jp
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hongo
authors.forename: Tamaki
authors.initials: T
authors.lastname: Matsuo
authors.forename: Junichi
authors.initials: J
authors.lastname: Kodama
authors.forename: Shin
authors.initials: S
authors.lastname: Ebara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.forename: Fernando
authors.initials: F
authors.lastname: Abrzua
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C414742:P53AIP1 protein, human; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases; C055645:hepsin; D020169:Caspases