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Modulation of Cell Growth and Gene Expression in LNCaP prostate cancer cells by 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)
Author(s) -
Wang WeiLin Winnie,
Russell Nicholas,
Chittur Sridar,
Ensslin Courtney,
MordanMcCombs Sarah,
Welsh JoEllen,
Tenniswood Martin
Publication year - 2009
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.23.1_supplement.lb281
Subject(s) - lncap , prostate cancer , bicalutamide , vitamin d and neurology , endocrinology , androgen receptor , calcitriol receptor , cancer research , testosterone (patch) , medicine , androgen , apoptosis , biology , programmed cell death , cancer , hormone , biochemistry
Epidemiological evidence suggests that vitamin D may be a potent chemopreventive agent for prostate cancer. It has been proposed that vitamin D can be used as a combination therapy with anti‐androgens for the treatment of early stage and locally invasive disease. In LNCaP cells, bicalutamide induces the rapid degradation of the androgen receptor (AR) and apoptosis in the presence or absence of testosterone. In the absence of testosterone, 1,25(OH) 2 D 3 has little or no effect on either parameter. However the effect of 1,25(OH) 2 D 3 is significantly altered in the presence of androgens. The AR is stabilized and cell death is abrogated. These results suggest that vitamin D mediated signaling interacts with AR mediated cell survival pathways, and reduces the efficacy of anti‐androgen therapy in hormone replete prostate cancer patients. Using genome‐wide microarray analysis, we have identified a set of genes that are differentially regulated by both vitamin D and testosterone. Most genes involved in cell cycle progression and apoptosis are not affected by both steroids. However, genes involved in the maintenance of intracellular calcium levels, such as TRPV6 are affected and may further influence the activity of various Ca 2+ responsive genes, including ANXA2 and STK17B. These suggest a novel calcium‐related anti‐apoptotic pathway that is unique to prostate cancer cells.