Hepsin inhibits the cell growth of endometrial cancer.
Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3sigma expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.
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
Takamoto
Norio
N
Abarzua
Fernando
F
Hongo
Atsushi
A
Kodama
Junichi
J
Nasu
Yasutomo
Y
Kumon
Hiromi
H
Hiramatsu
Yuji
Y
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D048948:14-3-3 Proteins; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases; C055645:hepsin