Estrogen receptor mutagenesis and hormone resistance.
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.
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Division of Medical Oncology, University of Texas Health Science Center, San Antonio 78284-78841.
D002478:Cells, Cultured; D004351:Drug Resistance; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D016296:Mutagenesis; D011960:Receptors, Estrogen / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology*
D011960:Receptors, Estrogen; D013629:Tamoxifen