Splicing Variants of Estrogen Receptor in Breast Cancer
Abstract
Results are summarized from the analysis of ER-a splicing variants in breast tumor cells. A highly diverse population of variants were observed representing primarily exon-skipped transcripts, but also including novel variants resulting from promiscuous or cryptic splicing. Techniques and reagents suited for the analysis of ER- alpha splicing variants were developed and described. Splicing variants were observed to be much more prevalent for ER-alpha than for most other genes including the progesterone receptor gene. The biochemical properties and transcriptional activities of the major ER-alpha splicing variants were also characterized. Two variants (ERDeltaE3 & ERDeltaE5) were identified that share significant residual function with intact ER-alpha. These properties confer on the ERDeltaE3 & ERDeltaE5 receptor variants the ability to inhibit the activity of some genes, but to stimulate the transcription of other genes. Genes that represent targets for induction by these ER-alpha splicing variants appear to lack consensus DNA-binding sites for ER-a, but instead they are regulated indirectly through interactions with other transcription factors such as AP-1. ER-alpha splicing variants thus function primarily through a recently proposed non-classical pathway for estrogen action. A variety of potential gene targets for regulation by the ERDeltaE3 & ERDeltaE5 variants are described.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA381693
Entities
People
- Richard J. Miksicek
Organizations
- State University of New York