Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.
Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. In a previous report, using an in vitro model, we found that the RET finger protein (RFP) (also known as tripartite motif-containing protein 27, TRIM27) confers cancer cell resistance to anticancer drugs. However, the significance of RFP expression in cancer patients remains elusive. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Consistent with clinical data, depletion of RFP by RNA interference (RNAi) in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular-targeted agent.
Department of Pathology, Nagoya University Graduate School of Medicine Nagoya, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Maiko
M
Horio
Takuya
T
Kato
Shinji
S
Mii
Atsushi
A
Enomoto
Masato
M
Asai
Naoya
N
Asai
Yoshiki
Y
Murakumo
Kiyosumi
K
Shibata
Fumitaka
F
Kikkawa
Masahide
M
Takahashi
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor; D016190:Carboplatin / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017239:Paclitaxel / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering; D017211:Treatment Failure; D023041:Xenograft Model Antitumor Assays; D000070584:Tripartite Motif Proteins
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016190:Carboplatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017239:Paclitaxel; D034741:RNA, Small Interfering; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins
Carboplatin; RET finger protein; chemoresistance; epithelial ovarian cancer; paclitaxel