REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer.
Human testicular cancer is very sensitive to chemotherapy and radiation therapy and is regarded as a curable cancer. The cancer prevails in the young reproductive generation and testicular dysfunction is often observed as a side effect, remaining a serious challenge. In the present study, we examined the potential utility of REIC/Dkk-3-based gene therapy against human testicular cancer. Expression of REIC/Dkk-3 was reduced in all of the human seminoma and non-seminomatous germ cell tumor tissues. Overexpression of REIC/Dkk-3 using an adenovirus vector (Ad-REIC) induced apoptosis in a testicular germ cell cancer cell line NCCIT but not in normal human fibroblasts. c-Jun terminal kinase (JNK) was activated by Ad-REIC and the induction of apoptosis was abrogated by a JNK inhibitor. A single intratumoral injection of Ad-REIC markedly inhibited the tumorigenic growth of NCCIT cells in nude mice. These results indicate that Ad-REIC may lead to developing less insulting and non-genotoxic therapeutic measures against human testicular cancer.
Tanimoto
Ryuta
R
Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Abarzua
Fernando
F
Sakaguchi
Masakiyo
M
Takaishi
Mikiro
M
Nasu
Yasutomo
Y
Kumon
Hiromi
H
Huh
Nam-Ho
NH
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018925:Chemokines; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013736:Testicular Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases