Inhibition of androgen action by dehydroepiandrosterone sulfotransferase transfected in PC-3 prostate cancer cells

Chan, Jeannie; Song, Chenchen; Matusik, Robert J.; Chatterjee, Bandana; Roy, Arun K.

doi:10.1016/s0009-2797(97)00138-5

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Furthermore, using a transiently transfected cell culture system, we have recently provided evidence that Std can attenuate androgen receptor function as reflected by the loss of androgen induction of the probasin gene promoter (11). This finding lends further credence to a physiological role of Std in modulating androgen sensitivity in selected target tissues.…”

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confidence: 60%

Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter

Song¹,

Jung²,

Kim³

et al. 1998

Journal of Biological Chemistry

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Dehydroepiandrosterone sulfotransferase (Std) catalyzes sulfonation of androgenic steroids and certain aromatic procarcinogens. In rats, this enzyme is selectively expressed in the liver, and its expression is strongly repressed by androgens. DNase I footprinting and electrophoretic mobility shift analyses revealed two hepatocyte nuclear factor-1 (HNF1), three CCAAT/enhancer-binding protein (C/EBP), and one consensus palindromic thyroid hormone response elements within the first 215 base pairs (bp) of the promoter sequence of rat Std. This promoter is normally inactive in fibroblastderived NIH 3T3 cells. However, overexpression of HNF1 and C/EBP resulted in synergistic activation of the Std promoter in this cell type, indicating essential roles of these two trans-regulators in liver-selective expression of the rat Std gene. On the other hand, point mutations at any one of five cis elements proximal to the ؊215 bp region markedly reduced reporter gene expression, suggesting that all of these sites are important for overall promoter function. Androgenic repression of the Std gene in rat liver can be recapitulated in androgen receptor (AR)-negative HepG2 hepatoma cells after cotransfection with an AR expression plasmid. Functional assay of a nested set of 5-deleted promoters mapped the negative androgen response region between positions ؊235 and ؊310. Antibody supershift and oligonucleotide competition identified three OCT-1 and two C/EBP elements between bp ؊231 and ؊292. An additional OCT-1 site was found to overlap with a C/EBP element at the ؊262/؊252 position. Mutational inactivation of any one of five cis elements within the ؊231/؊292 region abolished negative androgen response. However, none of these cis elements showed DNase I protection by recombinant AR in footprinting assay, suggesting the absence of a direct AR-DNA interaction. Thus, these studies on rat Std promoter function indicate that (i) HNF1 and C/EBP are responsible for liver specificity of the rat Std gene; (ii) androgenic repression of the gene requires the presence of all of the OCT-1 and C/EBP elements between positions ؊231 and ؊292; and (iii) AR may exert its negative regulatory effect indirectly through transcriptional interference of OCT-1 and C/EBP rather than through a direct DNA-AR interaction.

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confidence: 60%

Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter

Song¹,

Jung²,

Kim³

et al. 1998

Journal of Biological Chemistry

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“…Testosterone-dependent downregulation of STA2 in rodent hepatocytes is known from several previous studies (13,14,25,40) showing, e.g., fourfold-lower levels of STA2 mRNA in male than in female mice (14). STA2 encodes a cytosolic hydroxysteroid-specific sulfotransferase, which is involved in limiting the amount of active androgens in cells (12) and also in detoxification of cholestatic hydroxylated bile acids, such as lithocholic acid (23,36). In humans, low levels of hydroxysteroid sulfotransferase activity were shown to correlate with chronic liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis, chronic active hepatitis, and alcoholic cirrhosis (17).…”

Section: Discussionmentioning

confidence: 93%

Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria

et al. 2005

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Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-m-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an ϳ3-to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosteronemediated suppression of resistance against blood-stage malaria.

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“…Song et al (1998) reported that in rat liver, the binding of HNF1 factor with the promoter in the dehydroepiandrosterone sulfotransferase (Std) gene enables transcriptional activation of Std, which could repress androgenic steroids by catalyzing sulfonation. The Std gene is assumed not to be tissue-specific, since it was also found to modulate androgen sensitivity in a prostate cancer cell line (Chan et al, 1998). These lines of evidence strongly suggested that HNF1b is likely to be involved in prostate cancer in a manner associated with steroid hormone metabolism.…”

Section: Discussionmentioning

confidence: 99%

HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes

Zhong²,

Pang³

et al. 2013

Genet. Mol. Res.

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Inhibition of androgen action by dehydroepiandrosterone sulfotransferase transfected in PC-3 prostate cancer cells

Cited by 14 publications

References 24 publications

Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter

Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter

Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria

HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes

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