Fuqua S A
Division of Medical Oncology, University of Texas Health Science Center, San Antonio 78284-78841.
Cancer. 1994 Aug 1;74(3 Suppl):1026-9. doi: 10.1002/1097-0142(19940801)74:3+<1026::aid-cncr2820741509>3.0.co;2-k.
The authors have detected a truncated receptor that is lacking the majority of the hormone-binding domain because of the deletion of exon 5. This variant acts as a dominant-positive receptor in the absence of hormones. The exon 5 estrogen receptor (ER) variant, although originally identified in ER-negative, progesterone receptor-positive tumors, now has been found to be coexpressed at variable levels with the wild-type receptor in a large number of ER-positive tumors. Therefore, to establish the significance of its coexpression with the wild-type receptor, the authors transfected the variant into ER-positive MCF-7 cells. MCF-7 transfected cells that now express equivalent levels of the variant as compared with the wild-type receptor are resistant to the growth-inhibitory effects of tamoxifen. The authors hypothesize that the exon 5 ER deletion variant may be involved in clinical tamoxifen resistance and hormone independence.
作者检测到一种截短的受体，由于外显子5的缺失，该受体缺乏大部分激素结合结构域。这种变体在没有激素的情况下作为显性阳性受体发挥作用。外显子5雌激素受体（ER）变体虽然最初是在ER阴性、孕激素受体阳性肿瘤中发现的，但现在已发现在大量ER阳性肿瘤中与野生型受体以不同水平共表达。因此，为了确定其与野生型受体共表达的意义，作者将该变体转染到ER阳性的MCF-7细胞中。与野生型受体相比，现在表达同等水平变体的MCF-7转染细胞对他莫昔芬的生长抑制作用具有抗性。作者推测外显子5 ER缺失变体可能与临床他莫昔芬耐药性和激素非依赖性有关。
