IDENTIFICATION OF A VARIANT ESTROGEN-RECEPTOR LACKING EXON-4 AND ITS COEXPRESSION WITH WILD-TYPE ESTROGEN-RECEPTOR IN OVARIAN CARCINOMAS

By means of reverse transcription-PCR we have identified an alternativ ely spliced mRNA coding for a variant estrogen receptor (ER) that lack s exon 4 (ER Delta 4) and is coexpressed with the wild-type ER mRNA in ovarian carcinomas, Furthermore, Western blot analysis revealed the e xpression of the ER Delta 4 protein in normal as well as neoplastic ov arian tissues along with the wild-type ER, although the relative amoun ts of the wild-type ER and ER Delta 4 proteins varied. The trans-activ ational properties of this variant were studied in ER-negative COS1 ce ll lines by cotransfection of the ER Delta 4 expression vector and a r eporter gene containing the estrogen response element, The ER Delta 4 protein was not able to activate transcription of a reporter gene, How ever, it inhibited estrogen-dependent transcriptional activation in a dominant negative fashion when it was cotransfected with the wild-type ER and reporter plasmid, Because it has been shown that ER Delta 4 is not able to bind to its response element, the observed inhibitory eff ect probably occurs through protein-protein interactions, Although sev eral variants of the ER have been described from cancerous cells, none has been identified in ovarian tissues, and ER Delta 4 is the only is oform detected in normal tissues, These results may have implications for understanding the physiological role of ER Delta 4 in normal cells , because it may affect the function of the wild-type ER, depending on the level of the variant ER protein relative to that of the wild-type ER.