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Loss of the Vitamin D Receptor Accelerates Prostate Tumor Progression in LPB‐Tag Transgenic Mice
Author(s) -
MordanMcCombs Sarah,
Brown Ted,
Maurice Nick,
Welsh JoEllen,
Tenniswood Martin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a255-c
Subject(s) - calcitriol receptor , vitamin d and neurology , stromal cell , prostate cancer , tumor progression , prostate , endocrinology , medicine , parathyroid hormone , immunohistochemistry , genetically modified mouse , vitamin d deficiency , hormone , prostate specific antigen , cancer research , transgene , biology , cancer , calcium , gene , biochemistry
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.