Molecular Mechanism by which Retinoids Prevent Breast Cancer Development
Annual rept. 1 Jun 2004-31 May 2005
M D ANDERSON CANCER CENTER HOUSTON TX
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Retinoids are known for their ability to inhibit tumor growth and metastasis in breast cancer, indicating their promise for chemo-prevention and therapeutics. Retinoids exert their biological functions through two receptors, RAR and RXR. RXR-bound compounds rexinoid suppress ER-positive and ER-negative mammary tumors with reduced toxicity compared to RAR-bound compounds. Among RXR receptor isoforms, RXR alpha seems to play a critical role in tumor suppression. Thus, the authors focused on RXR alpha-specific ligand, Ro25-7328, to study whether this rexinoid suppresses breast cell growth. They found that Ro25-7328 suppressed the growth of both normal HMEC and T47D breast cancer cells. To identify the genes that are regulated by RXR alpha, they treated HMEC with Ro25-7328 and then examined changes in gene expression using affymetrix micro array. In HMEC, they identified 638 genes up-regulated and 347 genes down-regulated by Ro25-7328 with changes in fold induction more than 2 fold. Among them, they found several genes that are involved in cell death, cell growthmaintenance, signal transduction, and response to stimulus i.e., integrin beta4, integrin alpha6, BAX, E-cadherin, FOXO3A, paxillin, STAT3, and CD042. Further research on the influence of these genes on Ro25-7328-induced growth suppression would clarify the mechanism by which rexinoid suppresses breast cancer development.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research