Differentially expressed messenger RNA isoforms of the human estrogen receptor-α gene are generated by alternative splicing and promoter usage

Abstract

The isolation and characterization of several new human estrogen receptor-α (hERα) mRNAs are described. Together with those previously identified, they give rise to a total of six hERα mRNA isoforms (A-F hERα mRNAs). Produced from a single hERα 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 hERα mRNA isoforms revealed a differential pattern of expression of the hERα gene in human tissues and cell types. The A hERα 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 hERα mRNA isoforms, whereas the C and F hERα mRNA isoforms are the major forms detected in ovary. Finally, high levels of the E hERα mRNA isoform are restricted to the liver with an increased expression in females. Taken together, our results demonstrate that the hERα gene is a complex genomic unit exhibiting alternative splicing and promoter usage in a tissue-specific manner.