Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines.
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.
Nakamura
Keiichiro
K
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
Nasu
Yasutomo
Y
Hongo
Atsushi
A
Matsuo
Tamaki
T
Kodama
Junichi
J
Ebara
Shin
S
Nagai
Atsushi
A
Abrzua
Fernando
F
Kumon
Hiromi
H
Hiramatsu
Yuji
Y
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
D051017:Apoptosis Regulatory Proteins; C414742:P53AIP1 protein, human; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases; C055645:hepsin; D020169:Caspases