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p53 suppresses lung resistance-related protein expression through Y-box binding protein 1 in the MCF-7 breast tumor cell line.
- Source :
- Journal of Cellular Physiology; Dec2011, Vol. 226 Issue 12, p3433-3441, 9p, 1 Black and White Photograph, 1 Chart, 5 Graphs
- Publication Year :
- 2011
-
Abstract
- Lung resistance-related protein (LRP) has roles in multi-drug resistance of tumor cells. Understanding the mechanisms that regulate LRP expression in tumor cells is an important research area. A putative p53 response element in the LRP promoter has been found. Thus, p53-related regulation of LRP expression was explored in this study. We first demonstrated that p53 overexpression inhibited LRP expression both at the protein and mRNA levels. Then, using a dual-luciferase reporter assay, we located the p53 response element to the Y-box (−263∼−407) of the LRP promoter, the YB-1 binding site, but not the putative p53 response element. Furthermore, coimmunoprecipitation and chromatin immunoprecipitation showed p53 could bind to the Y-box of the LRP promoter through interaction of p53 with YB-1. YB-1 coexpression with p53 facilitated p53-induced suppression of endogenous LRP expression in MCF-7 cells. HDAC2, a corepressor of p53, was found to also interact with YB-1, and this interaction was mediated by p53. These results showed that the p53-HDAC2 transcriptional repressor complex can bind to the Y-box of the LRP promoter and repress LRP expression through interaction with YB-1. p53-related suppression of LRP expression was completely reversed by doxorubicin treatment and Adr, whereas CP and VP-16 treatment induced LRP expression increased significantly. Inhibition of LRP expression by siRNA facilitated Adr induced apoptosis of MCF-7 cells. All these findings indicated that loss of p53-related suppression of LRP may be the reason for LRP expression increase, and, therefore, chemotherapy resistance in tumor cells. J. Cell. Physiol. 226: 3433-3441, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 226
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 65803783
- Full Text :
- https://doi.org/10.1002/jcp.22700