Daaka Yehia
Department of Surgery and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Sci STKE. 2004 Jan 13;2004(216):re2. doi: 10.1126/stke.2162004re2.
Signal transduction research investigating mechanisms of androgen-independent prostate cancer cell proliferation has historically focused on the role of androgen and peptide growth factor receptors. More recent work has raised the idea that intracellular signaling mechanisms triggered by extracellular hormonal factors acting through heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can also mediate and sustain this pathologic process. Prostate cancer patients with advanced disease express elevated levels of GPCRs and GPCR ligands, suggesting that the GPCR system is activated in the cancerous gland and may contribute to tumor growth. Importantly, inhibition of G protein signaling attenuates prostate cancer cell growth in animal models. The nature of intracellular signaling pathways mediating mitogenic effects of GPCRs in prostate cancer is poorly defined, although the G protein-dependent activation of the Ras-to-mitogen-activated protein kinase pathway has emerged as a critical regulatory event. Activated GPCRs may also exert their mitogenic effects in the prostate by activating the androgen receptor.
历史上，研究雄激素非依赖性前列腺癌细胞增殖机制的信号转导研究一直聚焦于雄激素和肽生长因子受体的作用。最近的研究提出了这样一种观点，即由通过异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体（GPCR）起作用的细胞外激素因子触发的细胞内信号传导机制，也可以介导并维持这一病理过程。患有晚期疾病的前列腺癌患者表达的GPCR和GPCR配体水平升高，这表明GPCR系统在癌腺中被激活，可能有助于肿瘤生长。重要的是，在动物模型中，抑制G蛋白信号传导可减弱前列腺癌细胞的生长。尽管Ras到丝裂原活化蛋白激酶途径的G蛋白依赖性激活已成为一个关键的调节事件，但介导前列腺癌中GPCR促有丝分裂作用的细胞内信号通路的性质仍不清楚。活化的GPCR也可能通过激活雄激素受体在前列腺中发挥其促有丝分裂作用。
