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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2010

01-11-2010 | Preclinical study

UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugs

Authors: Wei Jin, Yang Liu, Si-guang Xu, Wen-jin Yin, Jun-jie Li, Jin-ming Yang, Zhi-ming Shao

Published in: Breast Cancer Research and Treatment | Issue 1/2010

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Abstract

Overexpression of MDR1 in breast cancer remains a major cause for the failure of chemotherapy. In the present report, we find UHRF1 plays an important role in inhibiting MDR1 promoter activity by directly binding to the MDR1 promoter. Knockdown of UHRF1 activates MDR1 promoter activity and expression, attenuates the binding of UHRF1 and HDAC1 to the MDR1 promoter. Overexpression of UHRF1 in NCI/ADR-RES cells can induce deacetylation of histones H3 and H4 on the MDR1 promoter, which is facilitated by recruitment of HDAC1 to the MDR1 promoter. Loss of histone acetylation is accompanied by loss of binding of the key transcription factor, MyoD, CBP and p300, locking in marked suppression of MDR1, increasing sensitivity of MDR cancer cells to cytotoxic drugs that are transported by P-glycoprotein (P-gp). The inhibition of MDR1 expression by UHRF1 may provide potential ways to overcome multidrug resistance (MDR) in breast cancer treatment.
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Metadata
Title
UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugs
Authors
Wei Jin
Yang Liu
Si-guang Xu
Wen-jin Yin
Jun-jie Li
Jin-ming Yang
Zhi-ming Shao
Publication date
01-11-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0683-8

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