Silva Corinne M, Shupnik Margaret A
Department of Medicine and Cancer Center, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Mol Endocrinol. 2007 Jul;21(7):1499-512. doi: 10.1210/me.2007-0109. Epub 2007 Apr 24.
The signaling pathways that are critical to the development and growth of breast cancer include those activated downstream of the estrogen receptor (ER) and the human epidermal growth factor receptor family. Many of these pathways, including the signal transducer and activator of transcription pathway, are common to both. The well-described genomic actions of ER involve its role as a transcription factor, either by binding directly to DNA through estrogen response elements, or by tethering to DNA through interaction with other proteins. Nongenomic signaling by the ER involves interaction with membrane-associated signaling proteins such as the c-Src tyrosine kinase and adapter proteins p130Cas and moderator of nongenomic activity of ER. Interactions with the signal transducer and activator of transcription pathway are important in both ER signaling pathways and are critical for estrogen-induced proliferation and tumorigenesis. These mechanisms of signaling cross talk and their role in resistance to antiestrogen therapies are discussed.
对乳腺癌的发生和发展至关重要的信号通路包括雌激素受体（ER）和人表皮生长因子受体家族下游激活的那些通路。其中许多通路，包括信号转导和转录激活通路，两者都有。ER 广为人知的基因组作用涉及其作为转录因子的角色，要么通过雌激素反应元件直接与 DNA 结合，要么通过与其他蛋白质相互作用与 DNA 相连。ER 的非基因组信号传导涉及与膜相关信号蛋白的相互作用，如 c-Src 酪氨酸激酶、衔接蛋白 p130Cas 以及 ER 非基因组活性调节剂。与信号转导和转录激活通路的相互作用在 ER 信号通路中都很重要，并且对于雌激素诱导的增殖和肿瘤发生至关重要。本文讨论了这些信号串扰机制及其在抗雌激素治疗耐药性中的作用。
