Ohlsson H, Lykkesfeldt A E, Madsen M W, Briand P
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen O.
Cancer Res. 1998 Oct 1;58(19):4264-8.
The estrogen receptor variant lacking exon 5 (ERdeltaE5) encodes a truncated protein that lacks the hormone-binding domain and has been suggested to be responsible for the estrogen-independent growth of human breast tumors and resistance to antiestrogen therapy. The biological function of the ERdeltaE5 in human breast epithelial cells has been studied by transient transfection of HMT-3522S1 cells with wild-type (wt) estrogen receptor (ER) and ERdeltaE5. A 10-fold higher expression of ERdeltaE5 mRNA compared to that of wt ER mRNA was found. However, the expression of ERdeltaE5 protein was significantly lower than the expression of wt ER protein. The ERdeltaE5 was unable to activate the transcription of an estrogen-responsive reporter gene in the absence as well as in the presence of estrogen. The ERdeltaE5 disclosed a dominant negative activity when expressed together with wt ER. These data indicate that the biological significance of ERdeltaE5 in human breast cancer is dubious.
缺少外显子5的雌激素受体变体（ERdeltaE5）编码一种截短的蛋白质，该蛋白质缺乏激素结合结构域，有人认为它与人类乳腺肿瘤的雌激素非依赖性生长以及对抗雌激素治疗的抗性有关。通过用野生型（wt）雌激素受体（ER）和ERdeltaE5瞬时转染HMT-3522S1细胞，研究了ERdeltaE5在人乳腺上皮细胞中的生物学功能。发现ERdeltaE5 mRNA的表达比wt ER mRNA高10倍。然而，ERdeltaE5蛋白的表达明显低于wt ER蛋白的表达。在不存在和存在雌激素的情况下，ERdeltaE5均无法激活雌激素反应性报告基因的转录。当与wt ER一起表达时，ERdeltaE5表现出显性负性活性。这些数据表明，ERdeltaE5在人类乳腺癌中的生物学意义值得怀疑。
