Regulation of REG4 Expression and Prediction of 5-Fluorouracil Sensitivity by CDX2 in Ovarian Mucinous Carcinoma

• Published in: Cancer genomics & proteomics Vol. 16; no. 6; pp. 481 - 490
• Main Authors: Koh, Iemasa, Nosaka, Suguru, Sekine, Masaki, Sugimoto, Jun, Hirata, Eiji, Kudo, Yoshiki
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.11.2019
• Subjects: 5-Fluorouracil; Adenocarcinoma, Mucinous - drug therapy; Adenocarcinoma, Mucinous - metabolism; Adenocarcinoma, Mucinous - pathology; Antineoplastic drugs; Antitumor agents; Apoptosis; CDX2 protein; CDX2 Transcription Factor - metabolism; Cell Line, Tumor; Chemotherapy; Drug Resistance, Neoplasm; Female; Fluorouracil - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Homeobox; Humans; MDR1 protein; Multidrug resistance; Neoplasm Proteins - metabolism; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; P-Glycoprotein; Paclitaxel; Pancreatitis-Associated Proteins - biosynthesis; Predictive Value of Tests; Resistance factors; Sensitivity analysis; Sensitivity enhancement; Transfection; Tumor cell lines; 5-fluorouracil; CDX2; mucinous carcinoma; ovarian cancer; REG4
• ISSN: 1109-6535; 1790-6245
• DOI: 10.21873/cgp.20151

The biological importance of the caudal-related homeobox transcription factor CDX2 in acquiring resistance to anticancer drugs has been studied in ovarian mucinous carcinoma. CDX2 promotes the expression of multidrug resistance 1 (MDR1) and confers resistance to paclitaxel. The regenerating islet-derived family member 4 (REG4) gene is a potential target gene of CDX2. In this study, we investigated the relationship between the expression of CDX2 and Reg IV and the regulation of Reg IV expression and examined novel chemotherapeutic regimens. The regulation of Reg IV expression by CDX2 and sensitivity of 5-fluorouracil (5-FU) were evaluated using ovarian mucinous cancer cell lines. The correlation of CDX2 with Reg IV expression was demonstrated in ovarian mucinous carcinoma. Reg IV expression was enhanced by transfection of CDX2 and was suppressed by inhibition of CDX2 expression. OMC-3 cells with ectopically overexpressed CDX2 showed enhanced apoptosis and sensitivity to 5-FU. CDX2 promotes resistance to paclitaxel and sensitivity to 5-FU. Novel 5-FU-based chemotherapy based on CDX2 may be used in ovarian mucinous carcinoma.