Identification of Cellular Binding Sites for a Novel
Abstract
We have synthesized a peptide, cAFPep, that stops the growth of ER+ human breast cancer. This peptide is derived from alpha fetoprotein (AFP), a safe, naturally-occurring protein produced during pregnancy which itself has anti-breast cancer activity. Although the anti-oncotic activity of this peptide and its precursors is well documented, the mechanism of its action has not been elucidated. An examination of the cellular binding proteins which had an affinity for the AFP-derived peptide was undertaken to probe the mechanism of action of this peptide. Members of the 70 kDa heat shock protein (HSP) family were found to bind with high affinity to the peptide. Furthermore, treatment with cAFPep reduced total cellular levels of ER, reduced the E2-stimulated phosphorylation of serine 118 of the ER, and reduced transcriptional activity of the ER. Taken together, these data suggest a mechanism of action of cAFPep that downregulates the ER by altering the interaction of ER with HSPs. Further understanding of the nature of the interactions with HSPs to alter the metabolism of the estrogen receptor will shed light on a novel pharmacological interference with estrogen particularly as it relates to prevention of estrogen-stimulated breast cancer growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA437620
Entities
People
- James A. Bennett
- Lori A. Defreest
Organizations
- Albany Medical College