Loss Of The Vitamin D Receptor Accelerates Prostate Tumor Progression In Lpb-Tag Transgenic Mice

Vitamin D has been associated in vitro with prevention and adjuvant treatment of breast and prostate cancer, but little in vivo work has been done to determine the role of the vitamin D receptor (VDR) and the vitamin D axis in prostate tumor progression. In this study, we investigate the progression of prostate tumors, from 7 wks to 18 wks of age, in the LPB-Tag transgenic mouse model with or without the VDR. Tumor progression was rated using a mouse-modified Gleason Score (MGS), evaluating epithelial and stromal proliferation. Further, levels of SV40 large T antigen expression and epithelial and stromal markers were determined at all time points by immunohistochemistry. Serum testosterone, parathyroid hormone, and vitamin D levels were also assessed to determine effective manipulation of the vitamin D axis by a high calcium (2.0%) rescue diet. VDR-null animals showed decreased time to progression, as determined by MGS rating, in comparison to VDR-WT animals. SV40 large T antigen expression remained consistent in both genotypes at all time points. Serum chemistry shows effective manipulation of the vitamin D axis in VDRWT animals, as determined by decreased PTH and vitamin D levels. Further study must be done to determine differences in gene expression in VDRKO and VDRWT animals, as well as stromal-epithelial interactions in the developing tumor.