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.