Identification of ten exon deleted ERbeta mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor beta mRNA is distinct from that of estrogen receptor alpha.

Four different human tissues and breast cancer cell lines were screened to identify exon deletion variant transcripts of estrogen receptor beta (ERbeta) by reverse transcription-polymerase chain reaction using the 'splice targeted primer approach' that amplifies each category of exon deleted variants as a separate gene population. A total of 10 different variant mRNAs that have deletions in various combination of exons were identified by sequence analysis. They were exon 2Delta; exons 2 and 5-6Delta; exon 3Delta; exon 4Delta; exon 5Delta; exons 5 and 2Delta; exon 6Delta; exons 6 and 2Delta; exons 6, 2-3Delta; and exons 5-6Delta. In some cases, deletion of an exon appears to be associated with a mutation of a specific base. Although ERalpha and ERbeta are highly homologous, have identical exon and functional domain organization, exhibit similar ligand-binding profiles and interact with identical DNA response elements, the sequence of exon skipping in ERbeta pre-mRNA appears to be distinct from that of ERalpha mRNA. Furthermore, results described here also suggest that alternate splicing of ERbeta mRNA is tissue specific. The presence of a ERbeta variant profile together with other ER isoforms in a tissue may have functional implications in binding and response to a particular ligand.