Crosstalk between androgen receptor and epidermal growth factor receptor-signalling pathways: a molecular switch for epithelial cell differentiation

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作者：

L Leotoing，M Manin，D Monte，S Baron，Y Communal，C Lours，G Veyssiere，L Morel，C Beaudoin

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摘要：

In the male, androgens promote and differentiation of sex reproductive organs through ligand activation of the (AR). Here, we show that androgens are not major actors of the associated with the differentiation process, and that the epidermal (EGF)-mediated interferes with AR activities to regulate androgen response when epithelial are differentiated. Higher AR expression and enhanced androgen responsiveness correlate with reduction of phosphorylated /2 over differentiation. These modifications are associated with recruitment of in phase G(0)/G(1), up-regulation of (kip1), down-regulation of () and , and accumulation of hypo-phosphorylated Rb. Exposure to EGF reduces AR expression levels and blocks androgen-dependent transcription in differentiated . It also restores and () levels, Rb hyper-, /2 activation and promotes re-entry as (kip1) levels are decreased. Treatment with a MEK inhibitor reverses the EGF-mediated AR down-regulation in differentiated , thus suggesting the existence of an inverse correlation between EGF and androgen in non-tumoural epithelia. Interestingly, when androgen is set in differentiated , exerts an inhibitory effect on activity but paradoxically does not modify (ErbB1) , indicating that androgens are able to disrupt the -cascade. Overall, our data demonstrate the existence of a balance between AR and activities that favours either the maintenance of differentiated conditions or the enhancement of capacities.

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关键词：

吡唑-5-酮硫代氨基脲晶体结构合成表征

DOI：

10.1677/JME-07-0021

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年份：

2007