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Coordinate regulation of lipogenic gene expression by androgens:
Evidence for a cascade mechanism involving sterol regulatory
element binding proteins
ABSTRACT To gain more insight into the molecular
mechanisms by which androgens stimulate lipogenesis and
induce a marked accumulation of neutral lipids in the human
prostate cancer cell line LNCaP, we studied their impact on
the expression of lipogenic enzymes. Northern blot analysis of
the steady-state mRNA levels of seven different lipogenic
enzymes revealed that androgens coordinately stimulate the
expression of enzymes belonging to the two major lipogenic
pathways: fatty acid synthesis and cholesterol synthesis. In
view of the important role of the recently characterized sterol
regulatory element binding proteins (SREBPs) in the coor-
dinate induction of lipogenic genes, we examined whether the
observed effects of androgens on lipogenic gene expression are
mediated by these transcription factors. Our findings indicate
that androgens stimulate the expression of SREBP tran-
scripts and precursor proteins and enhance the nuclear
content of the mature active form of the transcription factor.
Moreover, by using the fatty acid synthase gene as an exper-
imental paradigm we demonstrate that the presence of an
SREBP-binding site is essential for its regulation by andro-
gens. These data support the hypothesis that SREBPs are
involved in the coordinate regulation of lipogenic gene expres-
sion by androgens and provide evidence for the existence of a
cascade mechanism of androgen-regulated gene expression.
http://www.pnas.org/content/94/24/12975.full.pdf
Evidence for a cascade mechanism involving sterol regulatory
element binding proteins
ABSTRACT To gain more insight into the molecular
mechanisms by which androgens stimulate lipogenesis and
induce a marked accumulation of neutral lipids in the human
prostate cancer cell line LNCaP, we studied their impact on
the expression of lipogenic enzymes. Northern blot analysis of
the steady-state mRNA levels of seven different lipogenic
enzymes revealed that androgens coordinately stimulate the
expression of enzymes belonging to the two major lipogenic
pathways: fatty acid synthesis and cholesterol synthesis. In
view of the important role of the recently characterized sterol
regulatory element binding proteins (SREBPs) in the coor-
dinate induction of lipogenic genes, we examined whether the
observed effects of androgens on lipogenic gene expression are
mediated by these transcription factors. Our findings indicate
that androgens stimulate the expression of SREBP tran-
scripts and precursor proteins and enhance the nuclear
content of the mature active form of the transcription factor.
Moreover, by using the fatty acid synthase gene as an exper-
imental paradigm we demonstrate that the presence of an
SREBP-binding site is essential for its regulation by andro-
gens. These data support the hypothesis that SREBPs are
involved in the coordinate regulation of lipogenic gene expres-
sion by androgens and provide evidence for the existence of a
cascade mechanism of androgen-regulated gene expression.
http://www.pnas.org/content/94/24/12975.full.pdf