DIFFERENTIALLY EXPRESSED MESSENGER-RNA ISOFORMS OF THE HUMAN ESTROGENRECEPTOR-ALPHA GENE ARE GENERATED BY ALTERNATIVE SPLICING AND PROMOTER USAGE

The isolation and characterization of several new human estrogen recep tor-alpha (hER alpha) mRNAs are described. Together with those previou sly identified, they give rise to a total of six hER alpha mRNA isofor ms (A-F hER alpha mRNAs). Produced from a single hER alpha gene by mul tiple promoter usage, all these transcripts encode a common protein bu t differ in their 5'-untranslated region as a consequence of alternati ve splicing of five upstream exons (1B-1F). RT-PCR and S1 nuclease map ping analysis of these different hER alpha mRNA isoforms revealed a di fferential pattern of expression of the hER alpha gene in human tissue s and cell types. The A hER alpha mRNA is the main isoform detected in mammary glands or in the tumor cell lines derived from this tissue. I n endometrium, the predominant forms are the A and C hER alpha mRNA is oforms, whereas the C and F hER alpha mRNA isoforms are the major form s detected in ovary. Finally, high levels of the E hER alpha mRNA isof orm are restricted to the liver with an increased expression in female s. Taken together, our results;demonstrate that the hER alpha gene is a complex genomic unit exhibiting alternative splicing and promoter us age in a tissue-specific manner.