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 Google Scholar Google Scholar Articles by Ikeda, N. Articles by Kubota, Y. Search for Related Content PubMed PubMed Citation Articles by Ikeda, N. Articles by Kubota, Y.

Department of Urology, Graduate School of Medicine, Yokohama City University, Kanagawa 236-0004, Japan [N. I., H. U., H. I., M. Hos., Y. K.]; Department of Oral Pathology, Kanagawa Dental College, Kanagawa 238-8580, Japan [M. Hor.]; Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, Ishikawa 920-8641, Japan [S. K.]; and Departments of Nutritional Science [K-i. M.] and Clinical Nutrition [E. T.], School of Medicine, Tokushima University, Tokushima 770-8503, Japan

¹ To whom requests for reprints should be addressed, at Department of Urology, School of Medicine, Yokohama City University, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. E-mail: hu0428{at}med.yokohama-cu.ac.jp

The vitamin D₃ receptor, which is the nuclear receptor for 1,25-dihydroxyvitamin D₃ (VD₃), forms a heterodimer with the retinoid X receptor (RXR), which is the nuclear receptor for 9-cis-retinoic acid (9-cis-RA). The heterodimer binds to a specific response element consisting of two directly repeated pairs of motifs, AGGTGA, spaced by three nucleotides [direct repeat (DR) 3] and modulates the expression of VD₃-responsive genes. Telomerase activity, which is seen in most immortal cells and germ cells, is a complex of enzymes that maintain the length of telomeres. One of the major components of human telomerase, human telomerase reverse transcriptase (hTERT), is the catalytic subunit, and the expression of hTERT might correlate most strongly with telomerase activity. We found that the sequence of 5'-AGTTCATGGAGTTCA-3' (DR3') is similar to that of DR3 in the promoter region of hTERT. Our results showed that the combination of VD₃ and 9-cis-RA inhibited telomerase activity through direct interaction of the heterodimer of vitamin D₃ receptor and RXR with the DR3' sequence in the hTERT promoter as well as the combination of VD₃ and selective RXR ligand did. Also, in vivo data showed that the growth of xenografts in nude mice was inhibited by VD₃ and 9-cis-RA. The results of the present study provide evidence on the molecular mechanism of the inhibition of cell growth by these agents, and they could be novel therapeutic agents for prostate cancer.