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Influence of vitamin D on androgen receptor‐mediated signaling in LNCaP prostate cancer cells
Author(s) -
Rybarczyk Megan Michelle,
Russell Nicholas,
Mordan Lawrence,
Welsh JoEllen,
Tenniswood Martin
Publication year - 2008
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.22.1_supplement.637.2
Subject(s) - lncap , androgen receptor , prostate cancer , apoptosis , calcitriol receptor , endocrinology , medicine , signal transduction , androgen , cancer research , testosterone (patch) , programmed cell death , dihydrotestosterone , biology , receptor , chemistry , vitamin d and neurology , cancer , microbiology and biotechnology , hormone , biochemistry
The efficacy of the anti‐androgen Casodex relies on the interaction with the androgen receptor (AR). This study is designed to elucidate the interactions between AR signaling and the vitamin D receptor (VDR) signaling pathways. Using the LNCaP prostate cancer cell line as a model of early stage prostate cancer, we have shown that Casodex induces apoptosis in a time dependent manner which is co‐incident with the loss of the AR from the nucleus, in agreement with previous studies. While 1,25(OH) 2 D 3 induces apoptosis in this cell line in the absence of exogenous testosterone, in the presence of testosterone, treatment with 1,25(OH) 2 D 3 induces cell cycle arrest, but even at doses as high as 100 nM there is no evidence of apoptosis. Furthermore, in the presence of testosterone, 1,25(OH) 2 D 3 blocks the Casodex‐mediated degradation of the AR and abrogates the induction of apoptosis by Casodex. These data suggest that there is significant cross talk between the AR‐mediated signaling and VDR‐mediated signaling that influences the susceptibility of the cells to anti‐androgen induced cell death. Changes in the expression of several p73 isoforms, monitored by Western blotting, correlate with the sensitivity of the cells to Casodex, suggesting that the responsiveness of tumors to anti‐androgens may be inversely related to vitamin D status. (Supported by USPHS RO1 CA101114‐04 and the Coleman Foundation)