1194 CIRCULATING VITAMIN D3 AND INTRA-PROSTATIC CYP27B1 IN PROSTATE TUMORIGENESIS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research VI1 Apr 20101194 CIRCULATING VITAMIN D3 AND INTRA-PROSTATIC CYP27B1 IN PROSTATE TUMORIGENESIS Huei-Ju Ting, James Messing, Carla Beckham, Edward Messing, and Yi-Fen Lee Huei-Ju TingHuei-Ju Ting More articles by this author , James MessingJames Messing More articles by this author , Carla BeckhamCarla Beckham More articles by this author , Edward MessingEdward Messing More articles by this author , and Yi-Fen LeeYi-Fen Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.695AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epidemiological and preclinical studies suggest vitamin D3 is one of the nutrients effectively inhibiting prostate tumorigenesis. Unfortunately, the concern of systemic side effects from high doses of vitamin D3 limits its application in the general population. Defining the lowest amount of vitamin D3 uptake that can effectively prevent prostate tumorigenesis will establish a guideline for general healthy population. To translate the preventive effect of active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3 (1,25-VD) to clinical application, it is necessary to determine the effective dosage of the circulating form of vitamin D3, 25-hydroxyvitamin D3 (25-VD) in preventing tumorigenesis. CYP27B1 is the key enzyme converting 25-VD to 1,25-VD; therefore, this autocrine synthesis of 1,25-VD by prostate cells is one profound biochemical mechanism for the vitamin D chemopreventive action. The objective of this proposal is to determine the effective concentration of 25-VD in mediating the chemopreventive effect and elucidate intra-prostate CYP27B1 level as a new biomarker to predict individualism for prostate cancer development and behavior. METHODS The protein expression level of CYP27B1 was detected in several immortalized normal prostate cell lines. The transactivity of vitamin D receptor induced by different concentrations of 25-VD was measured by a reporter assay and Q-PCR which detects target gene expression. The effective concentration of 25-VD in preventing tumorigenesis was examined in carcinogen-induced prostate epithelial cell transformation models. The role of CYP27B1 in mediating the preventive effect of 25-VD was investigated by targeting knockdown of CYP27B1 using shRNA and human prostate tissue microarray (TMA). RESULTS The equivalent concentration of 25-VD that induced the same level of VDR transactivity as 100 nM of 1,25-VD was between 250-350 nM in these cell lines. This equivalent concentration of 25-VD could effectively prevent tumorigenesis in the parental non-malignant prostate epithelial cell line, but not in the CYP27B1 knockdown cell line. Human prostate TMA detected CYP27B1 expresseion in normal prostate, but not in the prostate cancer. CONCLUSIONS Here we defined the effective concentration of 25-VD and the role of CYP27B1 in preventing malignant-transformation of prostate epithelial cells. This study provides a guideline for future administration of vitamin D3 supplement and indicates that the individual variation of CYP27B1 expression level could contribute to the efficacy of vitamin D3 supplementation in preventing prostate cancer. Rochester, NY© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e462-e463 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Huei-Ju Ting More articles by this author James Messing More articles by this author Carla Beckham More articles by this author Edward Messing More articles by this author Yi-Fen Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...