| RRC ID |
51696
|
| 著者 |
Koh I, Hinoi T, Sentani K, Hirata E, Nosaka S, Niitsu H, Miguchi M, Adachi T, Yasui W, Ohdan H, Kudo Y.
|
| タイトル |
Regulation of multidrug resistance 1 expression by CDX2 in ovarian mucinous adenocarcinoma.
|
| ジャーナル |
Cancer Med
|
| Abstract |
Epithelial ovarian cancer is an aggressive gynecological malignancy with a high mortality rate. Resistance against chemotherapeutic agents often develops in ovarian cancer patients, contributing to high recurrence rates. The multidrug resistance 1 (MDR1/ABCB1) gene encodes P-glycoprotein, which affects the pharmacokinetic properties of anticancer agents. We previously reported that the Caudal-related homeobox transcription factor CDX2 transcriptionally regulates MDR1 expression in colorectal cancer. CDX2 is a factor that influences cancer cell differentiation, malignancy, and cancer progression. We hypothesized that profiling of CDX2 and MDR1 expression could be an effective strategy for predicting anticancer drug resistance. We studied the expression of these factors in clinical samples from ovarian cancer patients. We found that endogenous MDR1 expression was positively associated with CDX2 expression in ovarian mucinous adenocarcinoma. Using ovarian mucinous adenocarcinoma cell lines, we also observed decreased MDR1 expression following inhibition of CDX2 by RNA interference. In addition, CDX2 overexpression in MN-1 cells, which display low endogenous CDX2, resulted in upregulation of MDR1 expression. CDX2 induced MDR1-dependent resistance to vincristine and paclitaxel, which was reversed by treatment with the MDR1-specific inhibitor verapamil. Our findings show that CDX2 promotes upregulation of MDR1 expression, leading to drug resistance in ovarian mucinous adenocarcinoma. Therefore, our study demonstrates the potential of novel chemotherapy regimens based on CDX2 status and MDR1 expression in ovarian mucinous adenocarcinoma.
|
| 巻・号 |
5(7)
|
| ページ |
1546-55
|
| 公開日 |
2016-7-1
|
| DOI |
10.1002/cam4.697
|
| PMID |
27060927
|
| PMC |
PMC4944882
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Adenocarcinoma, Mucinous / genetics*
Adenocarcinoma, Mucinous / metabolism*
Adenocarcinoma, Mucinous / pathology
Antineoplastic Agents / pharmacology
CDX2 Transcription Factor / genetics
CDX2 Transcription Factor / metabolism*
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Drug Resistance, Neoplasm / genetics
Female
Gene Expression
Gene Expression Regulation, Neoplastic*
Humans
Neoplasms, Glandular and Epithelial / genetics
Neoplasms, Glandular and Epithelial / metabolism
Neoplasms, Glandular and Epithelial / pathology
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
RNA Interference
|
| IF |
3.491
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
OMC-3(RCB0755) |
