Molecular Cloning of Human and Rat Complementary DNA Encoding Androgen Receptors

Chang, Chawnshang; Kokontis, John M.; Liao, Shutsung

doi:10.1126/science.3353726

Cited by 844 publications

(353 citation statements)

References 31 publications

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“…The cDNA coding hAR was cloned into the pSG5 expression vector, as reported previously (Chang et al, 1988). The hAR deletion mutants D1, D2 and D3, lacking part of the prolinerich region spanning from 372 to 386 AA, were generated using in vitro site-directed mutagenesis.…”

Section: Constructsmentioning

confidence: 99%

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth

et al. 2007

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In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor (EGF) trigger association of the androgen receptor (AR)-estradiol receptor (ER) (a or b) complex with Src. This interaction activates Src and affects the G1 to S cell cycle progression. In this report, we identify the sequence responsible for the AR/Src interaction and describe a 10 amino-acid peptide that inhibits this interaction. Treatment of the human prostate or mammary cancer cells (LNCaP or MCF-7, respectively) with nanomolar concentrations of this peptide inhibits the androgen-or estradiol-induced association between the AR or the ER and Src the Src/Erk pathway activation, cyclin D1 expression and DNA synthesis, without interfering in the receptor-dependent transcriptional activity. Similarly, the peptide prevents the S phase entry of LNCaP and MCF-7 cells treated with EGF as well as mouse embryo fibroblasts stimulated with androgen or EGF. Interestingly, the peptide does not inhibit the S phase entry and cytoskeletal changes induced by EGF or serum treatment of AR-negative prostate cancer cell lines. The peptide is the first example of a specific inhibitor of steroid receptordependent signal transducing activity. The importance of these results is highlighted by the finding that the peptide strongly inhibits the growth of LNCaP xenografts established in nude mice.

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Section: Constructsmentioning

confidence: 99%

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth

et al. 2007

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“…AR belongs to the superfamily of nuclear receptors; in the presence of its ligands, it acts as a transcription factor [7], mediating signals that drive the development and differentiation of normal prostate epithelium [8]. In tumours, several mechanisms have been involved in the unavoidable progression to androgen independency, by which tumour cells evolve to bypass the ligand-dependent regulation of AR.…”

Section: Introductionmentioning

confidence: 99%

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Zhang¹,

Yang²,

Zheng³

et al. 2010

Asian J Androl

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The androgen receptor (AR) and its coregulators have important roles in the carcinogenesis of prostate cancer. p53 is an important tumour suppressor gene, and the absence of a fundamental p53 response may predispose to cancer. Transgelin, known as an ARA54-associated AR inhibitor, can suppress AR function in LNCaP cells. In addition to these effects, we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms, especially the interaction between transgelin and p53. Cell counting, flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin, we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.

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“…Androgens exert their biological effects through the androgen receptor (AR) (Chang et al, 1988), a member of the nuclear receptor superfamily (reviewed by Kastner et al, 1995;Mangelsdorf et al, 1995). One important target tissue of androgens and AR is the prostate.…”

Section: Introductionmentioning

confidence: 99%

Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation

et al. 2006

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The growth and progression of prostate cancer are dependent on androgens and androgen receptor (AR), which act by modulating gene expression. Utilizing a gene microarray approach, we have identified the a1-subunit gene of soluble guanylyl cyclase (sGC) as a novel androgen-regulated gene. A heterodimeric cytoplasmic protein composed of one a and one b subunit, sGC mediates the widespread cellular effects of nitric oxide (NO). We report here that, in prostate cancer cells, androgens stimulate the expression of sGCa1. A cloned human sGCa1 promoter is activated by androgen in an AR-dependent manner, suggesting that sGCa1 may be a direct AR target gene. Disruption of sGCa1 expression severely compromises the growth of both androgendependent and androgen-independent AR-positive prostate cancer cells. Overexpression of sGCa1 alone is sufficient for stimulating prostate cancer cell proliferation. Interestingly, the major growth effect of sGCa1 is independent of NO and cyclic guanosine monophosphate, a major mediator of the sGC enzyme. These data strongly suggest that sGCa1 acts in prostate cancer via a novel pathway that does not depend on sGCb1. Tissue studies show that sGCa1 expression is significantly elevated in advanced prostate cancer. Thus, sGCa1 may be an important mediator of the procarcinogenic effects of androgens.

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Molecular Cloning of Human and Rat Complementary DNA Encoding Androgen Receptors

Cited by 844 publications

References 31 publications

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation

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