ESR1
小结
ESR1是致癌基因，编码蛋白为雌激素受体α（ERα），是一种转录因子，属于核受体家族。ERα在性生殖发育和维持中起主要作用，特别是在雌性生殖器官中。ERα与雌激素结合后会诱导ERα的构象变化，允许该受体与HSP90解离并与其自身或ERβ二聚化，然后二聚体移到细胞核并且可以直接或者通过DNA中的雌激素反应元件（ERE）与靶基因的启动子和增强子结合，或者通过其他转录因子复合物如FOS/JUN/SP-1。一旦结合，雌激素受体就会募集调节ESR1靶基因转录的共调节因子，从而导致增殖，迁移和分化的变化。ESR1突变在原发性癌症中比较罕见（<5%），但是12-25％激素抵抗性转移性乳腺癌患者检测到在受体的LBD（受体配体结合域）会发生突变。Y537S and D538G是ESR1常见的耐药突变，并显示出对雌激素剥夺疗法获得抗性。
ESR1 gene encodes the estrogen receptor alpha (ERα) protein, which belongs to the family of nuclear receptors. ERα plays a major role in sexual reproductive development and maintenance, specifically in the female reproductive organs. Binding of the hormone estrogen, the ERα ligand, induces conformational changes to ERα, which allows the receptor to dissociate from HSP90 and dimerize with itself or ERβ. The dimer then translocates to the nucleus where it binds to promoters and enhancers of target genes either directly, via Estrogen Responsive Elements (ERE) in the DNA, or via other transcription factor complexes such as FOS/JUN/SP-1. Once bound, the estrogen receptor recruits co-regulators that modulate the transcription of ESR1 target genes, resulting in changes in proliferation, migration and differentiation. While mutations in ESR1 are generally very rare in primary cancers (<5%), a number of mutations occurring in the ligand-binding domain (LBD) of the receptor were identified in ~12-25% of hormone-resistant metastatic breast cancer patients. The most recurrent mutations, Y537S and D538G, result in a constitutively active receptor, which is shown to confer acquired resistance to estrogen deprivation therapies.