Cross-talk between the androgen receptor and the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer.
Cross-talk between the androgen receptor and the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer.
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DOI：
10.2174/156800907781662248
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发表时间：
2007-08
影响因子：
3
通讯作者：
Yu Wang;J. Kreisberg;P. Ghosh
中科院分区：
文献类型：
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作者：
Yu Wang;J. Kreisberg;P. Ghosh
前列腺癌最初依赖于雄激素生长;因此，复发性前列腺采用雄激素消融治疗，这可能导致进展为雄激素非依赖性，其特征为对此类治疗产生耐药性。雄激素结合并激活雄激素受体（AR），雄激素受体是转录因子的核类固醇受体家族的成员，其调节前列腺癌细胞在雄激素非依赖性以及依赖性肿瘤中的增殖和存活。另一种调节增殖和存活的途径是磷脂酰肌醇3-激酶（PI 3 K）/Akt途径。在这里，我们分析了文献中的报告表明，这两个途径合作，以调节前列腺肿瘤的发展和进展。研究表明，AR的转录活性和表达受Akt的调控。此外，雄激素通过基因组和非基因组效应调节Akt通路。这解释了为什么前列腺肿瘤接受雄激素消融后Akt磷酸化增加，并表明肿瘤用另一种途径补偿一种途径的损失。这两种途径之间的相互作用的不同模式，包括直接相互作用，或通过下游中间体，如wnt/GSK-3 β/β-连环蛋白途径，NF-κ B和转录因子的FOXO家族的调节，将进行讨论。此外，我们还将讨论Akt在AR与Akt磷酸化的上游调节因子（如EGF和IGF-1受体家族的受体酪氨酸激酶和肿瘤抑制因子PTEN）相互作用中的作用。
Prostate cancer is initially dependent on androgens for growth; hence, recurrent prostate is treated with androgen ablation which may result in progression to androgen independence characterized by a resistance to such therapy. Androgens bind to and activate the androgen receptor (AR), a member of the nuclear steroid receptor family of transcription factors, which regulates prostate cancer cell proliferation and survival in androgen-independent, as well as -dependent, tumors. Another pathway regulating proliferation and survival is the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Here we analyze reports in the literature indicating that these two pathways cooperate to regulate prostate tumor development and progression. Studies show that AR transcriptional activity and expression are regulated by Akt. In addition, androgens regulate the Akt pathway by both genomic and non-genomic effects. This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3beta/beta-catenin pathway, NF-kappaB, and the FOXO family of transcription factors, will be discussed. In addition, we will discuss the role of Akt in the interaction of the AR with upstream regulators of Akt phosphorylation, such as receptor tyrosine kinases of the EGF and IGF-1 receptor families and the tumor suppressor PTEN.