Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone

Wolf, Dieter A; Kohlhuber, Franz; Schulz, Peter; Fittler, Friedrich; Eick, Dirk

doi:10.1038/bjc.1992.76

Cited by 41 publications

(27 citation statements)

References 51 publications

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“…This seemed reasonable since the incomplete disappearance of hAR RNA even after prolonged hormone administration could reflect a differential effect of MIB on individual RNA start sites. We have recently observed differential effects of MIB on the promoter usage of the c-myc protooncogene in LNCaP cells (34). Figure 2A confirms the results of previous reports showing that hAR gene expression in several cell types uses two principal mRNA initiation sites located 1115 and 1126 nucleotides in front of the ATG translation initiation codon.…”

Section: Ar Rnas Starting From Different Transcription Initiation Sitsupporting

confidence: 80%

“…possible participation of the AR protein in hAR RNA down-regulation by MIB, we tried to antagonize the androgen effect by the simultaneous addition of AR blocking agents (antiandrogens). The steroidal antiandrogen cyproterone acetate (CA) as well as the nonsteroidal antiandrogen hydroxy flutamide (Flu-OH) were recently shown to effectively prevent the inhibitory action of MIB on proliferation and c-myc expression in LNCaP cells (34,35) while not exerting any effect when administered alone. Due to the relatively low affinity of antiandrogens for the AR a several hundredfold molar excess over the androgen is required for effective blockage of androgen action (36).…”

Section: Ar Rnas Starting From Different Transcription Initiation Sitmentioning

confidence: 99%

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Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Wolf¹,

Herzinger²,

Hermeking³

et al. 1993

Molecular Endocrinology

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Autoregulation is a control mechanism common to several proteins of the steroid/thyroid hormone receptor superfamily. In this work the effect of androgens and antiandrogens on the expression of the human androgen receptor (hAR) in prostate and breast cancer cell lines was studied. Northern blot analysis revealed a decrease in hAR steady state RNA levels in LNCaP cells by 3.3 nht of the synthetic androgen mibolerone. Maximal down-regulation of hAR RNA to 30% of control levels occurred 48 h after hormone addition. T47D breast cancer cells showed a similar effect with mibolerone, while hAR expression in normal skin fibroblasts did not respond to androgen treatment. As shown by nuclease Sl analysis, hAR transcripts initiate at three principal start sites, all of which are equally sensitive to androgen. Steroidal as well as nonsteroidal antiandrogens were capable of partially antagonizing androgen-mediated hAR RNA down-regulation in LNCaP and T47D cells, while not exerting a significant effect when administered alone. While hAR RNA stability was increased by hormone, nuclear run-on analysis revealed a 4-fold reduction of hAR gene transcrip tion 98 h after androgen treatment. Although decreased hAR RNA levels did not coincide with a parallel decrease in AR protein levels, analysis of androgen-inducible reporter constructs demonstrated that prolonged androgen administration to ceils results in a progressively impaired sensitivity of the intracellular androgen response mechanism. These results show that prolonged androgen exposure leads, besides its effect on hAR RNA levels, to functional inactivation of the AR. Thus, in viva, posttranslational control of AR activity appears to be a novel mechanism of negative autoregulation of androgen effects on gene expression. (Molecular Endocrinology

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Section: Ar Rnas Starting From Different Transcription Initiation Sitsupporting

confidence: 80%

Section: Ar Rnas Starting From Different Transcription Initiation Sitmentioning

confidence: 99%

Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Wolf¹,

Herzinger²,

Hermeking³

et al. 1993

Molecular Endocrinology

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“…On the other hand, in various cell types and tissues, c-myc expression has been shown to be regulated by sex-steroid hormones (Schuchard et al 1993). For example, testosterone treatment reduces c-myc mRNA level, in vivo, in the rat ventral prostate (Quarmby et al 1987) and, in vitro, in human prostatic cells (Wolf et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Modulation of rat preadipocyte adipose conversion by androgenic status: involvement of C/EBPs transcription factors

Garcı́a

Lacasa²,

Agli³

et al. 1999

Journal of Endocrinology

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Androgenic status affects rat preadipocyte adipose conversion from two deep intra-abdominal (epididymal and perirenal) fat depots differently. The aim of this study was to establish whether these site-specific alterations of adipogenesis are related to altered expressions of the transcriptional factors regulating proliferation and differentiation of preadipocytes, c-myc and CCAAT/enhancer binding proteins (C/EBPs: C/EBP and ).The increased proliferation of epididymal and perirenal preadipocytes from castrated rats was not linked to variations in c-myc mRNA and protein levels.The expression of the early marker of adipogenesis, lipoprotein lipase (LPL), was decreased by androgenic deprivation in epididymal cells but remained insensitive to the androgenic status in perirenal preadipocytes. In contrast, LPL expression increased in subcutaneous preadipocytes from castrated rats, an effect which was partly corrected by testosterone treatment.Expression of C/EBP was unaffected by androgenic status whatever the anatomical origin of the preadipocytes. In contrast, the mRNA and protein levels of C/EBP were greatly decreased by androgenic deprivation in epididymal cells, an alteration which could not be corrected by in vivo testosterone administration.Altogether these results demonstrated that in preadipocytes androgenic deprivation affects site-specifically the expression of LPL, an early marker of adipogenesis and of C/EBP , a master regulator of adipogenesis. These observations contribute to an explanation of why castration induces defective adipose conversion in rat epididymal preadipocytes specifically.

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“…43 This transcription factor is involved in differentiation and the level of C-MYC mRNA is higher in proliferating cells. 44 Levels fall dramatically when cells withdraw from the cell cycle or undergo terminal differentiation. 44 A gene that is involved in these cellular processes might be involved in tumourigenesis if its function is altered, particularly by amplification.…”

Section: The C-myc Oncogenementioning

confidence: 99%

“…44 Levels fall dramatically when cells withdraw from the cell cycle or undergo terminal differentiation. 44 A gene that is involved in these cellular processes might be involved in tumourigenesis if its function is altered, particularly by amplification. A number of studies have shown that C-MYC mRNA is elevated in PC, compared to BPH or normal prostate tissue, and there tends to be enhanced expression with higher-grade tumours.…”

Section: The C-myc Oncogenementioning

confidence: 99%

Molecular biology of prostate cancer

Karayi

Markham

2004

Prostate Cancer Prostatic Dis

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Development of any cancer reflects a progressive accumulation of alterations in various genes. Oncogenes, tumour suppressor genes, DNA repair genes and metastasis suppressor genes have been investigated in prostate cancer. Here, we review current understanding of the molecular biology of prostate cancer. Detailed understanding of the molecular basis of prostate cancer will provide insights into the aetiology and prognosis of the disease, and suggest avenues for therapeutic intervention in the future.

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Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone

Cited by 41 publications

References 51 publications

Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Modulation of rat preadipocyte adipose conversion by androgenic status: involvement of C/EBPs transcription factors

Molecular biology of prostate cancer

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