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Androgen‐mediated cholesterol metabolism in LNCaP and PC‐3 cell lines is regulated through two different isoforms of acyl‐coenzyme A: Cholesterol Acyltransferase (ACAT)
Author(s) -
Locke Jennifer A.,
Wasan Kishor M.,
Nelson Colleen C.,
Guns Emma S.,
Leon Carlos G.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20674
Subject(s) - lncap , sterol o acyltransferase , endocrinology , medicine , androgen , androgen receptor , cholesterol , reductase , biology , prostate cancer , chemistry , enzyme , biochemistry , cancer , lipoprotein , hormone
BACKGROUND The objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification in androgen‐sensitive (AS) prostate cancer (LNCaP) cells. METHODS We investigated the activity and expression of cholesterol metabolism enzymes, HMG‐CoA‐reductase and ACAT in the LNCaP and PC‐3 (androgen‐independent control) models. RESULTS Microsomal PC‐3 HMG‐CoA‐reductase activity was increased with R1881 despite having similar cholesterol levels while increased cholesterol levels in microsomes from LNCaPs treated with R1881 (L+) were associated with increased HMG‐CoA reductase activity. Increased intracellular cholesteryl esters (CE) found in (L+) were not associated with an increased ACAT1 activity. There was no effect from androgen treatment on ACAT1 protein expression in theses cells; however, ACAT2 expression was induced upon R1881 treatment. In contrast, we found an increase in the in vitro ACAT1 activity in PC‐3 cells treated with androgen (P+). Only ACAT1 expression was induced in P+. We further assessed the expression of STAT1α, a transcriptional activator that modulates ACAT1 expression. STAT1α expression and phosphorylation were induced in P+. To determine the role of the AR on ACAT1 expression and esterification, we treated PC‐3 cells overexpressing the androgen receptor with R1881 (PAR+). AR expression was decreased in PAR+ cells; ACAT1 protein expression and cholesterol ester levels were also decreased, however, ACAT2 remained unchanged. STAT1α expression was decreased in PAR+. CONCLUSIONS Overall, these findings support the importance of cholesterol metabolism regulation within prostate cancer cells and unravel a novel role for STAT1α in prostate cancer metabolism. Prostate 68: 20–33, 2008. © 2007 Wiley‐Liss, Inc.