FUNCTIONAL-ANALYSIS OF AN ALTERNATIVELY SPLICED ESTROGEN-RECEPTOR LACKING EXON-4 ISOLATED FROM MCF-7 BREAST-CANCER CELLS AND MENINGIOMA TISSUE

An alternatively spliced mRNA coding for a variant estrogen receptor ( ER) missing exon 4 (ER Delta 4) was detected in the breast tumor cell line MCF7 and meningioma tissue by using the reversed transcriptase PC R technique. The trans-activational properties of this mutant ER were assessed in embryo carcinoma P19EC and human choriocarcinoma JEG3 cell s by co-transfection of the ER Delta 4 expression vector with an oxyto cin promoter construct containing an estrogen-responsive element. ER D elta 4 did not trans-activate the oxytocin promoter in either a hormon e-dependent or -independent manner. Co-transfection of ER Delta 4 toge ther with the wtER did not show any interference of ER Delta 4 on the stimulation of the oxytocin promoter by the wtER. ER Delta 4 was trans lated in vitro. Its capacity to bind estradiol, and the binding of the variant to a synthetic estrogen-responsive element were compared to t hose of the wild-type receptor. ER Delta 4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ER Del ta 4 appears to be a silent variant and we speculate that it is withou t any role in tumor progression.