CBP-dependent Wnt/beta-catenin Signaling is Crucial in Regulation of MDR1 Transcription
文献类型：期刊论文
| 作者 | Xia, Zanxian1,2; Guo, Mingquan3; Liu, Han4; Jiang, Luwei1,2; Li, Qiaoxia5,6; Peng, Jian7; Li, Jia-Da1,2; Shan, Baoen5,6; Feng, Pinghui8; Ma, Hong9 |
| 刊名 | CURRENT CANCER DRUG TARGETS
 |
| 出版日期 | 2015 |
| 卷号 | 15期号:6页码:519-532 |
| 关键词 | CBP Chromatin Immunoprecipitation MDR1 p300 RNAi Wnt/beta-catenin |
| ISSN号 | 1568-0096 |
| 英文摘要 | Aberrant expression of the MDR1-encoded P-glycoprotein (P-gp) is often associated with clinical multi-drug resistance (MDR) leading to poor prognosis and failure of chemotherapy. However, the precise and cooperative molecular mechanism responsible for MDR1 transcription and expression in acquired MDR remains elusive. We, herein, demonstrate that Wnt/beta-catenin signal pathway is constitutively activated in Doxorubicin-induced MDR cancer cells, in which nuclear beta-catenin specifically interacts with the transcriptional coactivator CBP in a MEK1/2/ERK1/2 signal-dependent manner. Specific knockdown of both beta-catenin and CBP by RNAi-mediated depletion abrogates MDR1 transcription and expression resulting in a complete reversal of P-gp-dependent efflux function and restoration of sensitivity to the Doxorubincin-induced cytotoxicity. Moreover, following pharmacological disruption of CBP and beta-catenin interaction through inhibition of the MEK1/2/ERK1/2 signal by the specific inhibitor PD98059, MDR1 transcription and its encoded P-gp-dependent function are abolished. These findings conclude that the CBP/beta-catenin complex is a core component of the MDR1 transcriptional "enhancesome". |
| 资助项目 | scientific research foundation of Central South University in China |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000359252500009 |
| 出版者 | BENTHAM SCIENCE PUBL LTD |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/327]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Xia, Zanxian |
| 作者单位 | 1.Cent S Univ, State Key Lab Med Genet, Changsha 410013, Hunan, Peoples R China 2.Cent S Univ, Sch Life Sci, Changsha 410013, Hunan, Peoples R China 3.Chinese Acad Sci, Wuhan Bot Garden, Key Lab Plant Germplasm Enhancement & Specialty A, Wuhan, Hubei, Peoples R China 4.Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA 5.Hebei Med Univ, Hosp 4, Canc Res Ctr, Shijiazhuang, Hebei, Peoples R China 6.Hebei Canc Inst, Shijiazhuang, Hebei, Peoples R China 7.Cent S Univ, Xiangya Hosp, Natl Hepatobiliary & Enter Surg Res Ctr, Changsha 410013, Hunan, Peoples R China 8.Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA 9.Univ So Calif, Childrens Hosp Los Angeles, Dept Hematol & Oncol, Los Angeles, CA 90089 USA |
| 推荐引用方式 GB/T 7714 | Xia, Zanxian,Guo, Mingquan,Liu, Han,et al. CBP-dependent Wnt/beta-catenin Signaling is Crucial in Regulation of MDR1 Transcription[J]. CURRENT CANCER DRUG TARGETS,2015,15(6):519-532. |
| APA | Xia, Zanxian.,Guo, Mingquan.,Liu, Han.,Jiang, Luwei.,Li, Qiaoxia.,...&Ma, Hong.(2015).CBP-dependent Wnt/beta-catenin Signaling is Crucial in Regulation of MDR1 Transcription.CURRENT CANCER DRUG TARGETS,15(6),519-532. |
| MLA | Xia, Zanxian,et al."CBP-dependent Wnt/beta-catenin Signaling is Crucial in Regulation of MDR1 Transcription".CURRENT CANCER DRUG TARGETS 15.6(2015):519-532. |
入库方式： OAI收割
来源：武汉植物园
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