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The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice

Authors :
Jamal Hill
Yong Li
Yun Zhang
Reid P. Bissonnette
William W. Lamph
Powel H. Brown
Hee Tae Kim
Qiang Shen
Source :
British Journal of Cancer
Publication Year :
2008
Publisher :
Springer Science and Business Media LLC, 2008.

Abstract

Retinoids, vitamin A analogues that bind to retinoic acid receptor (RAR) or retinoid X receptor (RXR), play important roles in regulating cell proliferation, apoptosis, and differentiation. Recently, RXR-selective ligands, also referred to as rexinoids, have been investigated as potential chemopreventive agents for breast cancer. Our previous studies demonstrated that the rexinoid bexarotene significantly prevented ER-negative mammary tumourigenesis with less toxicity than naturally occurring retinoids in animal models. To determine whether bexarotene prevents cancer at the early stages during the multistage process of mammary carcinogenesis, we treated MMTV-erbB2 mice with bexarotene for 2 or 4 months. The development of preinvasive mammary lesions such as hyperplasias and carcinoma-in-situ was significantly inhibited. This inhibition was associated with reduced proliferation, but no induction of apoptosis. We also examined the regulation of a number of rexinoid-modulated genes including critical growth and cell cycle regulating genes using breast cell lines and mammary gland samples from mice treated with rexinoids. We showed that two of these genes (DHRS3 and DEC2) were modulated by bexarotene both in vitro and in vivo. Identification of these rexinoid-modulated genes will help us understand the mechanism by which rexinoid prevents cancer. Such rexinoid-regulated genes also represent potential biomarkers to assess the response of rexinoid treatment in clinical trials.

Details

ISSN :
15321827 and 00070920
Volume :
98
Database :
OpenAIRE
Journal :
British Journal of Cancer
Accession number :
edsair.doi.dedup.....d5054d8f2d4703641c7f06322885e167
Full Text :
https://doi.org/10.1038/sj.bjc.6604320