Fuqua S A, Allred D C, Auchus R J
University of Texas Health Science Center, Department of Medicine, San Antonio 78284.
J Cell Biochem Suppl. 1993;17G:194-7. doi: 10.1002/jcb.240531135.
Recent data suggest that the expression of estrogen receptor (ER) variants may be common in clinical breast cancer. The significance of their expression is complicated by the fact that they are often coexpressed with wild-type ER in the same tumor. We have focused upon one such ER variant which lacks exon 5 within the hormone binding domain of the receptor. This deletion introduces a stop codon, resulting in a truncated ER of 40 kDa which is unable to bind hormone. We have been exploring the hypothesis that this variant may contribute to clinical antiestrogen resistance. Coexpression of the exon 5 variant along with wild-type ER in MCF-7 human breast cancer cells confers resistance to the commonly used antiestrogen, tamoxifen. In addition, we have observed that some metastatic breast lesions overexpress exon 5 ER deletional variant transcripts. We conclude that differences in the relative amounts of several ER variants in the same tumor may interact to determine hormonal responsiveness and metastatic behavior.
近期数据表明，雌激素受体（ER）变体的表达在临床乳腺癌中可能很常见。它们表达的意义因常与野生型ER在同一肿瘤中共表达这一事实而变得复杂。我们专注于一种这样的ER变体，其在受体的激素结合域内缺少外显子5。这种缺失引入了一个终止密码子，导致产生一个40 kDa的截短型ER，它无法结合激素。我们一直在探索这一变体可能导致临床抗雌激素耐药性的假说。外显子5变体与野生型ER在MCF-7人乳腺癌细胞中共表达会赋予对常用抗雌激素他莫昔芬的耐药性。此外，我们观察到一些转移性乳腺病变过度表达外显子5 ER缺失变体转录本。我们得出结论，同一肿瘤中几种ER变体相对量的差异可能相互作用，以决定激素反应性和转移行为。
