Dipartimento di Patologia Generale, II Università di Napoli, Via L. De Crecchio 7, 80138 Naples, Italy.
Steroids. 2010 Aug-Sep;75(8-9):524-7. doi: 10.1016/j.steroids.2009.10.007. Epub 2009 Oct 30.
Estrogen receptor (ER) is a ligand-regulated transcription factor that controls human breast cancer cell proliferation. About 60-70% of human breast cancers express ER. In spite of major progress in the therapy of human breast cancer, many patients become resistant to pharmacologic treatments and develop metastatic breast tumors. Several mechanisms have been proposed to explain tumor progression and resistance to the therapies. However, the causes of hormone-dependent breast tumor progression as well as therapy resistance are still debated. An increasing body of evidence from our and other laboratories shows that in breast cancer cells, in addition to its classical transcriptional action, ER stimulates proliferative and anti-apoptotic signaling pathways in response to either ligand binding or growth factors. This discovery has led to the synthesis of new compounds specifically interfering in the rapid responses mediated by ER. It also suggests that the modalities currently in use for breast cancer treatment need to be reconsidered.
雌激素受体（ER）是一种配体调节转录因子，控制着人类乳腺癌细胞的增殖。大约 60-70%的人类乳腺癌表达 ER。尽管在人类乳腺癌的治疗方面取得了重大进展，但许多患者对药物治疗产生耐药性，并发展为转移性乳腺癌。已经提出了几种机制来解释肿瘤的进展和对治疗的耐药性。然而，激素依赖性乳腺癌进展和治疗耐药的原因仍存在争议。我们和其他实验室的越来越多的证据表明，在乳腺癌细胞中，除了其经典的转录作用外，ER 还能通过配体结合或生长因子刺激增殖和抗凋亡信号通路。这一发现导致了专门干扰 ER 介导的快速反应的新化合物的合成。这也表明，目前用于乳腺癌治疗的方法需要重新考虑。
