This Article Full Text Full Text (PDF) 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 Fukuchi, J. Articles by Liao, S. Search for Related Content PubMed PubMed Citation Articles by Fukuchi, J. Articles by Liao, S.

Antiproliferative Effect of Liver X Receptor Agonists on LNCaP Human Prostate Cancer Cells

The Ben May Institute for Cancer Research and The Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois

Liver X receptors function as central transcriptional regulators for lipid homeostasis, for which agonists have been developed as potential drugs for treatment of cardiovascular diseases and metabolic syndromes. Because dysregulation of lipid metabolism has been implicated in sex hormone-dependent cancers, we investigated the effect of liver X receptor agonists on prostate and breast cancer cell proliferation. Treatment of human prostate cancer LNCaP cell lines with the synthetic liver X receptor agonist T0901317 decreased the percentage of S-phase cells in a dose-dependent manner and increased the expression of cyclin-dependent kinase inhibitor p27^Kip-1 (p27). Knockdown of p27 by RNA interference blocks T0901317-induced growth inhibition, suggesting that p27 expression plays a crucial role in this signaling. Liver X receptor agonists also inhibited the proliferation of other prostate and breast cancer cell lines. The level of liver X receptor expression correlated directly with sensitivity to growth inhibition by liver X receptor agonists. Retroviral expression of liver X receptor in human breast cancer MDA-MB435S cells, which express low levels of endogenous liver X receptors and are insensitive to T0901317, sensitized these cells to T0901317. Consistent with our observations in LNCaP cells, T0901317 induces dramatic up-regulation of p27 in liver X receptor –overexpressing MDA-MB435S cells. Furthermore, oral administration of T0901317 inhibited the growth of LNCaP tumors in athymic nude mice. Based on these results, modulation of the liver X receptor signaling pathway is a new target for controlling tumor cell proliferation; therefore, liver X receptor agonists may have utility as antitumorigenic agents.

This article has been cited by other articles:

				J. Hoon Lee, H. Gong, S. Khadem, Y. Lu, X. Gao, S. Li, J. Zhang, and W. Xie Androgen Deprivation by Activating the Liver X Receptor Endocrinology, August 1, 2008; 149(8): 3778 - 3788. [Abstract] [Full Text] [PDF]

				M. Nilsson, K. Dahlman-Wright, C. Karelmo, J.-A. Gustafsson, and K. R. Steffensen Elk1 and SRF transcription factors convey basal transcription and mediate glucose response via their binding sites in the human LXRB gene promoter Nucleic Acids Res., July 10, 2007; (2007) gkm492v1. [Abstract] [Full Text] [PDF]

				I. B. Jeffery, S. F. Madden, P. A. McGettigan, G. Perriere, A. C. Culhane, and D. G. Higgins Integrating transcription factor binding site information with gene expression datasets Bioinformatics, February 1, 2007; 23(3): 298 - 305. [Abstract] [Full Text] [PDF]

				C.-p. Chuu, R. A. Hiipakka, J. M. Kokontis, J. Fukuchi, R.-Y. Chen, and S. Liao Inhibition of Tumor Growth and Progression of LNCaP Prostate Cancer Cells in Athymic Mice by Androgen and Liver X Receptor Agonist. Cancer Res., July 1, 2006; 66(13): 6482 - 6486. [Abstract] [Full Text] [PDF]