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Differentially Expressed Messenger RNA Isoforms of the Human Estrogen Receptor- Gene Are Generated by Alternative Splicing and Promoter Usage

European Molecular Biology Laboratory (G.F., V.S-B., F.G.) D-69117, Heidelberg, Germany
National Diagnostic Centre (C.G., M.K.) University College Galway, Ireland

The isolation and characterization of several new human estrogen receptor- (hER) mRNAs are described. Together with those previously identified, they give rise to a total of six hER mRNA isoforms (A–F hER mRNAs). Produced from a single hER gene by multiple promoter usage, all these transcripts encode a common protein but differ in their 5'-untranslated region as a consequence of alternative splicing of five upstream exons (1B–1F). RT-PCR and S1 nuclease mapping analysis of these different hER mRNA isoforms revealed a differential pattern of expression of the hER gene in human tissues and cell types. The A hER mRNA is the main isoform detected in mammary glands or in the tumor cell lines derived from this tissue. In endometrium, the predominant forms are the A and C hER mRNA isoforms, whereas the C and F hER mRNA isoforms are the major forms detected in ovary. Finally, high levels of the E hER mRNA isoform are restricted to the liver with an increased expression in females. Taken together, our results demonstrate that the hER gene is a complex genomic unit exhibiting alternative splicing and promoter usage in a tissue-specific manner.

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