Sluyser M
Department of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
Crit Rev Oncog. 1994;5(6):539-54.
Breast tumors that have become resistant to endocrine therapy have been found to contain estrogen receptor (ER) variants due to aberrant splicing mechanisms of the ER gene. Exon skipping can give rise to dominant-positive receptors that are transcriptionally active in the absence of estrogen, or dominant-negative receptors that are themselves transcriptionally inactive but prevent the action of the normal receptor. ER splice variants similar to those in breast cancer have also been reported in human meningiomas. Androgen receptor (AR) variants have been detected in some prostate cancers that exhibit resistance to androgen therapy. In leukemia and lymphoma, mutations in the glucocorticoid receptor (GR) cause resistance to cell lysis by dexamethasone. Thus, there is increasing evidence that mutations in the genes of steroid receptors can cause loss of hormone dependency in different cancer types.
已发现对内分泌治疗产生耐药性的乳腺肿瘤因雌激素受体（ER）基因异常剪接机制而含有ER变体。外显子跳跃可产生在无雌激素情况下具有转录活性的显性阳性受体，或本身无转录活性但可阻止正常受体发挥作用的显性阴性受体。在人类脑膜瘤中也报道了与乳腺癌中类似的ER剪接变体。在一些对雄激素治疗有抗性的前列腺癌中检测到雄激素受体（AR）变体。在白血病和淋巴瘤中，糖皮质激素受体（GR）的突变导致对地塞米松诱导的细胞裂解产生抗性。因此，越来越多的证据表明，类固醇受体基因的突变可导致不同癌症类型中激素依赖性丧失。
