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 Ikezoe, T. Articles by Koeffler, H. P. Search for Related Content PubMed PubMed Citation Articles by Ikezoe, T. Articles by Koeffler, H. P.

CCAAT/Enhancer-Binding Protein : A Molecular Target of 1,25-Dihydroxyvitamin D₃ in Androgen-Responsive Prostate Cancer LNCaP Cells

¹ Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, California; ² Department of Internal Medicine, Kochi Medical School, Kochi, Japan; and ³ Leo Pharmaceuticals, Ballerup, Denmark

Requests for reprints: Takayuki Ikezoe, Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. Phone: 81-88-880-2345; Fax: 81-88-880-2348; E-mail: ikezoet{at}med.kochi-ms.ac.jp.

1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃], the active metabolite of vitamin D₃, inhibits the proliferation of prostate cancer cells. However, the molecular mechanisms by which 1,25(OH)₂D₃ inhibits the proliferation of these cells remain to be fully elucidated. In this study, we used microarray technology to identify target genes of 1,25(OH)₂D₃ in androgen-responsive prostate cancer LNCaP cells. 1,25(OH)₂D₃ up-regulated CCAAT/enhancer-binding protein (C/EBP) by 5-fold in these cells. Knockdown of C/EBP expression by RNA interference showed that C/EBP is essential for the significant growth inhibition of LNCaP cells in response to 1,25(OH)₂D₃ treatment. Moreover, we found that 1,25(OH)₂D₃ induced C/EBP in other cancer cells, including the estrogen receptor (ER)–expressing MCF-7 and T47D breast cancer cells that are sensitive to the growth inhibitory effects of 1,25(OH)₂D₃. On the other hand, 1,25(OH)₂D₃ was not able to induce C/EBP in either androgen receptor–negative PC-3 and DU145 or ER-negative breast cancer MDA-MB-231 cells that were relatively resistant to growth inhibition by 1,25(OH)₂D₃. Furthermore, forced expression of C/EBP in prostate cancer LNCaP as well as breast cancer MCF-7 and T47D cells dramatically reduced their clonal growth. Taken together, forced expression of C/EBP in cancer cells may be a promising therapeutic strategy.

This article has been cited by other articles:

				Y. Xu, F. Fang, D. K. St. Clair, S. Josson, P. Sompol, I. Spasojevic, and W. H. St. Clair Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1{alpha},25-dihydroxyvitamin D3 in prostate cancer cells Mol. Cancer Ther., July 1, 2007; 6(7): 2048 - 2056. [Abstract] [Full Text] [PDF]

				M. Thangaraju, M. Rudelius, B. Bierie, M. Raffeld, S. Sharan, L. Hennighausen, A-M. Huang, and E. Sterneck C/EBP{delta} is a crucial regulator of pro-apoptotic gene expression during mammary gland involution Development, November 1, 2005; 132(21): 4675 - 4685. [Abstract] [Full Text] [PDF]