This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, H.-T. Articles by Brown, P. H. Search for Related Content PubMed PubMed Citation Articles by Kim, H.-T. Articles by Brown, P. H.

Identification of Biomarkers Modulated by the Rexinoid LGD1069 (Bexarotene) in Human Breast Cells Using Oligonucleotide Arrays

¹ Breast Center, Baylor College of Medicine, Houston, Texas; ² Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, California; and ³ National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Powel H. Brown, Breast Center, Baylor College of Medicine, One Baylor Plaza, MS 600, Houston, TX 77030. Phone: 713-798-1609; Fax: 713-798-1642; E-mail: pbrown{at}bcm.tmc.edu.

Retinoids have been found to be promising chemopreventive agents that play an important role in regulating cell growth, differentiation, and apoptosis. The action of retinoids is mediated by retinoid receptors (retinoic acid receptors and retinoid X receptors), which are nuclear transcription factors that, when bound to retinoids, regulate gene expression. LGD1069 is a highly selective RXR agonist that has reduced toxicity compared with retinoids. Our previous studies have shown that RXR-selective ligands (or "rexinoids"), including LGD1069, can inhibit the growth of normal and malignant breast cells and can suppress the development of breast cancer in transgenic mice. For the current study, we attempted to identify biomarkers of the chemopreventive effect of the RXR-selective retinoid LGD1069. In these experiments, we used Affymetrix microarrays to identify target genes that were modulated by LGD1069 in normal human breast cells. Affymetrix and dChip analysis identified more than 100 genes that were up-regulated or down-regulated by LGD1069 treatment. We then tested 16 of these genes in validation experiments using quantitative reverse transcription-PCR and Western blotting of independently prepared samples, and found that 15 of 16 genes were modulated in a similar manner in these validation experiments as in the microarray experiments. Genes found to be regulated include known retinoid-regulated genes, growth regulatory genes, transcription factors, and differentiation markers. We then showed that the expression of several of these rexinoid-regulated biomarkers is modulated in vivo in mammary glands from mice treated with LGD1069. These critical growth-regulating proteins will be promising targets of future agents for the prevention and treatment of breast cancer. (Cancer Res 2006; 66(24): 12009-18)

This article has been cited by other articles:

				M. C. Abba, Y. Hu, C. C. Levy, S. Gaddis, F. S. Kittrell, J. Hill, R. P. Bissonnette, P. H. Brown, D. Medina, and C. M. Aldaz Identification of Modulated Genes by Three Classes of Chemopreventive Agents at Preneoplastic Stages in a p53-Null Mouse Mammary Tumor Model Cancer Prevention Research, February 1, 2009; 2(2): 175 - 184. [Abstract] [Full Text] [PDF]

				T. E. Strecker, Q. Shen, Y. Zhang, J. L. Hill, Y. Li, C. Wang, H.-T. Kim, T. M. Gilmer, K. R. Sexton, S. G. Hilsenbeck, et al. Effect of Lapatinib on the Development of Estrogen Receptor-Negative Mammary Tumors in Mice J Natl Cancer Inst, January 21, 2009; 101(2): 107 - 113. [Abstract] [Full Text] [PDF]

				I. P. Uray, Q. Shen, H.-S. Seo, H. Kim, W. W. Lamph, R. P. Bissonnette, and P. H. Brown Rexinoid-induced Expression of IGFBP-6 Requires RAR{beta}-dependent Permissive Cooperation of Retinoid Receptors and AP-1 J. Biol. Chem., January 2, 2009; 284(1): 345 - 353. [Abstract] [Full Text] [PDF]

				F. Pettersson, N. Hanna, M. Lagodich, D. Dupere-Richer, M.-C. Couture, C. Choi, and W. H. Miller Jr. Rexinoids Modulate Steroid and Xenobiotic Receptor Activity by Increasing Its Protein Turnover in a Calpain-dependent Manner J. Biol. Chem., August 8, 2008; 283(32): 21945 - 21952. [Abstract] [Full Text] [PDF]

				P. H. Brown, K. Subbaramaiah, A. P. Salmon, R. Baker, R. A. Newman, P. Yang, X. K. Zhou, R. P. Bissonnette, A. J. Dannenberg, and L. R. Howe Combination Chemoprevention of HER2/neu-Induced Breast Cancer Using a Cyclooxygenase-2 Inhibitor and a Retinoid X Receptor-Selective Retinoid Cancer Prevention Research, August 1, 2008; 1(3): 208 - 214. [Abstract] [Full Text] [PDF]

				L. R. Howe Rexinoids and Breast Cancer Prevention Clin. Cancer Res., October 15, 2007; 13(20): 5983 - 5987. [Full Text] [PDF]

				K. Liby, D. B. Royce, R. Risingsong, C. R. Williams, M. D. Wood, R. A. Chandraratna, and M. B. Sporn A New Rexinoid, NRX194204, Prevents Carcinogenesis in Both the Lung and Mammary Gland Clin. Cancer Res., October 15, 2007; 13(20): 6237 - 6243. [Abstract] [Full Text] [PDF]