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 Δ4) was detected in the breast tumor cell line MCF7 and meningioma tissue by using the reversed transcriptase PCR technique. The trans-activational properties of this mutant ER were assessed in embryo carcinoma P19EC and human choriocarcinoma JEG3 cells by co-transfection of the ER Δ4 expression vector with an oxytocin promoter construct containing an estrogen-responsive element. ER Δ4 did not trans-activate the oxytocin promoter in either a hormone-dependent or -independent manner. Co-transfection of ER Δ4 together with the wtER did not show any interference of ER /gDA4 on the stimulation of the oxytocin promoter by the wtER. ER Δ4 was translated in vitro. Its capacity to bind estradiol, and the binding of the variant to a synthetic estrogen-responsive element were compared to those of the wild-type receptor. ER Δ4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ER Δ4 appears to be a silent variant and we speculate that it is without any role in tumor progression.