Giovannelli Pia, Di Donato Marzia, Giraldi Tiziana, Migliaccio Antimo, Castoria Gabriella, Auricchio Ferdinando
Department of General Pathology - II University of Naples- Via L. De Crecchio, 7, 80138 Napoli, Italy.
Front Biosci (Elite Ed). 2012 Jan 1;4(1):453-61. doi: 10.2741/e390.
Human breast and prostate cancers are complex diseases caused by the progressive accumulation of gene mutations combined with epigenetic deregulation of critical genes and derangement of signaling pathways. Compelling evidence indicates that steroid hormones elicit non-genomic responses in cytoplasm of target cells. In this cellular location, steroid-coupled receptors recruit signaling effectors or scaffold proteins, thereafter activating multiple pathways leading to proliferation, survival, migration and invasiveness. Thus, the immediate challenge is the dissection of key upstream events regulating steroid response in target tissues to prevent progression and improve treatment of breast and prostate cancers. Progress in our understanding of the molecular mechanisms that play a master role in these cancers has strongly stimulated the search for specific inhibitors of key signaling molecules. This review aims to give an up-to-date report of the complex network regulating non-genomic action of steroid hormones in target cells. The final section highlights recent advances from our laboratory and future directions in alternative approaches for the treatment of breast and prostate cancers.
人类乳腺癌和前列腺癌是复杂的疾病，由基因突变的逐步积累、关键基因的表观遗传失调以及信号通路紊乱引起。有力证据表明，类固醇激素在靶细胞的细胞质中引发非基因组反应。在这个细胞位置，类固醇偶联受体招募信号效应器或支架蛋白，进而激活多条导致增殖、存活、迁移和侵袭的通路。因此，当前的紧迫挑战是剖析调节靶组织中类固醇反应的关键上游事件，以防止乳腺癌和前列腺癌进展并改善其治疗。我们对在这些癌症中起主要作用的分子机制的理解取得的进展，有力地推动了对关键信号分子特异性抑制剂的寻找。本综述旨在提供关于调节类固醇激素在靶细胞中非基因组作用的复杂网络的最新报告。最后一部分重点介绍了我们实验室的最新进展以及乳腺癌和前列腺癌治疗替代方法的未来方向。
