Migliaccio A, Castoria G, Di Domenico M, De Falco A, Bilancio A, Auricchio F
Istituto di Patologia Generale e Oncologia, Seconda Università di Napoli, 80138 Naples, Italy.
Ann N Y Acad Sci. 2002 Jun;963:185-90. doi: 10.1111/j.1749-6632.2002.tb04109.x.
Recent observations that steroids use pathways universally known to be regulated by growth factors and interleukins highlight the following points: (1) Steroid stimulation of the canonical pathway Src/Ras/Erk signaling from membrane to nuclei or its single members has been observed in different cell types including human cancer-derived cells, neurons, osteoblasts, osteocytes, and endothelial cells. This stimulation has been reconstituted and analyzed in transiently transfected cells. (2) Cellular context and intracellular localization of receptors are crucial in determining the biological effects evoked by this hormonal stimulation: proliferation, protection from apoptosis, and vasorelaxation. (3) Classical steroid receptors localized in the extranuclear compartment directly and, in some cases, simultaneously interact with Src. They are capable of unexpected cross talks responsible for the observed effects. (4) Other signaling pathways including P13K/AKT are also stimulated by steroids. The aim of future work will be to arrive at an integrated general view of the different signaling pathways activated by steroids and to analyze the concert between these pathways and the hormonal transcriptional action. This general view should be simultaneously verified in different cell contexts, under different physiologic and pathologic conditions. We expect that the new technologies, above all gene and protein microarray, will make this goal feasible.
最近的观察结果表明，类固醇使用的途径普遍已知受生长因子和白细胞介素调节，这突出了以下几点：（1）在包括人类癌症衍生细胞、神经元、成骨细胞、骨细胞和内皮细胞在内的不同细胞类型中，已观察到类固醇对从膜到细胞核的经典途径Src/Ras/Erk信号传导或其单个成员的刺激。这种刺激已在瞬时转染细胞中进行了重组和分析。（2）细胞背景和受体的细胞内定位对于确定这种激素刺激所引发的生物学效应（增殖、抗凋亡和血管舒张）至关重要。（3）定位于核外区室的经典类固醇受体直接且在某些情况下同时与Src相互作用。它们能够进行意想不到的相互作用，从而导致观察到的效应。（4）包括P13K/AKT在内的其他信号通路也受到类固醇的刺激。未来工作的目标将是对类固醇激活的不同信号通路形成一个综合的总体认识，并分析这些通路与激素转录作用之间的协同作用。这一总体认识应在不同的细胞背景、不同的生理和病理条件下同时得到验证。我们预计，最重要的是基因和蛋白质微阵列等新技术将使这一目标可行。
