Mutant p53 cooperates with ETS2 to promote etoposide resistance

• Type of Material: Article
• Authors: Phi M. Do, University of Mississippi Cancer Institute; Lakshman Varanasi, University of Mississippi Cancer Institute; Songqing Fan, Emory University; Chunyang Li, Emory University; Iwona Kubacka, University of Texas Medical Branch; Virginia Newman, University of Mississippi Cancer Institute; Krishna Chauhan, University of Mississippi Cancer Institute; Silvano Rakeem Daniels, University of Mississippi Cancer Institute; Maurizio Boccetta, Loyola University Chicago; Michael R. Garrett, University of Mississippi Cancer Institute; Runzhao Li, Emory University; Luis A. Martinez, University of Mississippi Cancer Institute
• Language: English
• Date: 2012-04-15
• Publisher: Cold Spring Harbor Laboratory Press
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by Cold Spring Harbor Laboratory Press
• Final Published Version (URL): http://dx.doi.org/10.1101%2Fgad.181685.111
• Title of Journal or Parent Work: Genes and Development
• ISSN: 0890-9369
• Volume: 26
• Issue: 8
• Start Page: 830
• End Page: 845
• Keywords: p53; TDP2; cancer
• Research Categories: Health Sciences, Oncology

Abstract

Cancer cell resistance to chemotherapy is a major problem in the treatment of cancer. Mutant p53 is associated with several gain-of-function behaviors, such as chemotherapy resistance, deregulated cell growth, inhibition of apoptosis, and increased cell motility and invasion. The transcriptional mechanism by which mutant p53 regulates chemotherapy resistance is not well understood. In this study by Martinez and colleagues, the authors identified TDP2 as a transcriptional target of mutant p53. TDP2 is an enzyme exhibiting 5′-tyrosyl DNA phosphodiesterase activity and is involved in the resistance to etoposide. In addition, the authors demonstrated a significant correlation between the overexpression of TDP2 and mutant p53 in human lung cancer. Thus, this study provides insight into a novel target for mutant p53 that promotes chemotherapy resistance.