Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 杜健华教授 (药剂学院) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1158/1541-7786.MCR-10-0270 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/22WOS source URL
其它资讯
摘要Histone deacetylase inhibitors (HDACI) are promising anticancer agents and their use in combination with conventional anticancer drugs is currently under investigation. We previously reported cell line-specific upregulation of ABCG2, a multidrug resistance transporter shown to control oral bioavailability and CNS penetration, by the HDACI romidepsin, although the precise mechanism in a particular cell line remains to be determined. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by numerous environmental contaminants and has been shown to be a client protein of heat shock protein 90 (Hsp90). A xenobiotic response element was defined in the ABCG2 promoter and was shown to mediate AhR signaling. Activated AhR was found to be associated with the ABCG2 promoter only in cell line models that respond to romidepsin with ABCG2 upregulation. Our data suggest that romidepsin acetylated Hsp70 and inhibited the chaperone function of Hsp90, thereby allowing the dissociation of AhR from Hsp90. The dissociation of AhR from Hsp90 may be a prerequisite for the differential upregulation of ABCG2 by romidepsin. Increasing our understanding of the mechanism(s) governing differential upregulation of ABCG2 in response to romidepsin could provide an insight into strategies needed to tackle resistance to HDACIs in cancer therapeutics. Mol Cancer Res; 9(4); 516-27. (C) 2011 AACR.
着者To KKW, Robey R, Zhan ZR, Bangiolo L, Bates SE
期刊名称Molecular Cancer Research
出版年份2011
月份4
日期1
卷号9
期次4
出版社American Association for Cancer Research
页次516 - 527
国际标準期刊号1541-7786
电子国际标準期刊号1557-3125
语言英式英语
Web of Science 学科类别Cell Biology; CELL BIOLOGY; Oncology; ONCOLOGY
