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The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice
- 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.
- Subjects :
- Cancer Research
medicine.medical_specialty
Tetrahydronaphthalenes
rexinoid
Mammary gland
Mice, Transgenic
ER negative
Biology
Retinoid X receptor
Mice
breast cancer
MMTV-erbB2
Mammary Glands, Animal
prevention
Mammary tumor virus
Cyclin D
Cyclins
Internal medicine
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
Anticarcinogenic Agents
Cell Proliferation
Homeodomain Proteins
Bexarotene
Cell growth
Gene Expression Profiling
bexarotene
Mammary Neoplasms, Experimental
Cancer
Genes, erbB-2
Cell cycle
medicine.disease
Retinoic acid receptor
Endocrinology
medicine.anatomical_structure
Mammary Tumor Virus, Mouse
Oncology
Cancer research
Female
Translational Therapeutics
Precancerous Conditions
medicine.drug
Subjects
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