title: Dietary vitamin D and vitamin D receptor level modulate epithelial cell proliferation and apoptosis in the prostate.
abstract: Low vitamin D (VD) status may increase prostate cancer risk but experimental evidence for this relationship is modest. We tested whether low VD status or VD receptor (VDR) deletion influences prostate epithelial cell (PEC) biology using intact mice, castrated mice, or castrated mice treated with testosterone propionate (TP, 2.5 mg/kg BW). PEC proliferation (Ki-67 staining) and apoptosis (TUNEL method) were determined in the anterior prostate (AP). In study 1, wild-type (WT) and TgAPT(121) mice (a model of prostate intraepithelial neoplasia) were fed diets with 25, 200 (reference diet), or 10,000 IU VD/kg diet (as vitamin D(3)) prior to castration/repletion. Serum 25 hydroxyvitamin D levels were 26, 78, and 237 nmol/L in the three diet groups, respectively. Castration reduced proliferation and increased apoptosis in the AP while TP reversed these effects. Low VD diet increased proliferation in WT (+82%) and TgAPT(121) (+24%) mice while it suppressed apoptosis in WT (-29%) and TgAPT(121) (-37%) mice. This diet also increased the severity of prostate intraepithelial neoplastic lesions in the AP of intact TgAPT(121) mice. In study 2, mice with PEC-specific VDR deletion (PEC VDR KO) were examined after castration/repletion. TUNEL staining was 60% lower in castrated PEC VDR KO mice compared with castrated WT mice. In castrated mice given TP, Ki-67 staining was 2-fold higher in PEC VDR KO compared with WT mice. Our data show that low diet VDR or VDR deletion provide a prostate environment that is permissive to early procarcinogenic events that enhance prostate cancer risk.
authors.affiliation: Center for Cancer Research, Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana, USA. pavelk@msu.edu
authors.forename: Pavlo L
authors.initials: PL
authors.lastname: Kovalenko
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun-Ge
authors.initials: JG
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.forename: James C
authors.initials: JC
authors.lastname: Fleet
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000097:blood; D002369:Castration; D049109:Cell Proliferation; D002478:Cells, Cultured; D004032:Diet; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000502:physiology*; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D000728:Androgens; D018167:Receptors, Calcitriol; D014807:Vitamin D; D002118:Calcium