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 (ERdelta4) 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 ERdelta4 expression vector with an oxytocin promoter construct containing an estrogen-responsive element. ERdelta4 did not trans-activate the oxytocin promoter in either a hormone-dependent or -independent manner. Co-transfection of ERdelta4 together with the wtER did not show any interference of ERdelta4 on the stimulation of the oxytocin promoter by the wtER. ERdelta4 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. ERdelta4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ERdelta4 appears to be a silent variant and we speculate that it is without any role in tumor progression.
Koehorst
S G
SG
Department of Endocrinology, Academic Hospital Utrecht, Netherlands.
Cox
J J
JJ
Donker
G H
GH
Lopes da Silva
S
S
Burbach
J P
JP
Thijssen
J H
JH
Blankenstein
M A
MA
D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008579:Meningioma / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004967:Estrogens; D011960:Receptors, Estrogen