Factors that Effect Signal Transduction by the Estrogen Receptor.
Abstract
This project examines the mechanism of signal transduction by the estrogen receptor (ER), a hormone dependent transcriptional regulator involved in many human breast tumors. We have found that ectopic expression of the cyclin A/cdk2 kinase complex increases hormone-dependent transcriptional activity by the estrogen receptor in vivo. This effect can be further enhanced by the concurrent expression of cyclin-dependent kinase activators, CAKs, and abolished by coexpression of the cdk inhibitor (CDI), p27. Likewise, ER-dependent transcriptional activation is reduced by the expression of a dominant negative cdk2 mutant in mammalian cells or by deletion of a potential cyclin A homologue, Clb4, in yeast. ER is also phosphorylated in vitro by cyclin A/cdk2 and incorporation of phosphate into ER is stimulated by the ectopic expression of cyclin A in vivo. Together, these results strongly suggest a role for cyclin-dependent kinases in the regulation of ER transcriptional enhancement.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1995
- Accession Number
- ADA311359
Entities
People
- Michael J. Garabadian
Organizations
- NYU Langone Health