Identification of ten exon deleted ERβ mRNAs in human ovary, breast, uterus and bone tissues:: alternate splicing pattern of estrogen receptor β mRNA is distinct from that of estrogen receptor α

Four different human tissues and breast cancer cell fines 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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.