Summer Research

* Student(s): Andeu Viader Valls
Advisor: Stephen Festin

Title: Regulation of estrogen receptor activity by a newly developed cyclic AFP9-mer peptide in an estrogen response element (ERE) based luciferase reporter system


AFP is a protein produced in the fetus and found in the maternal serum during pregnancy. This protein has been shown capable of blocking the hormone stimulated growth of ER expressing breast cancer cell lines both in vivo and in vitro. The active site of AFP is confined to an eight amino acid segment present in the domain III of the protein. Several peptide analogs of this 8 amino-acid segment have been developed in an attempt to create an 8-mer peptide which maintains the biological activity of the full protein but possesses a longer shelf-life. Recently, a more stable analog (cyc-E-Ornithine-TOVNOGQ) was developed but no extensive testing of its activity had been carried out. We tested the new AFP 8-mer peptide in ER negative liver cancer cells (HepG2 cells) containing a full-length ER-? expressing plasmid and an artificial reporter (EREII-tk-Luc). In this model, previously developed AFP peptide analogs with proved biological activity consistently stimulated transcription. The results obtained show that the new peptide is able to increase transcription in this system by about 50% when present at a concentration of 10-5 molar. However, no stimulation was induced at lower concentrations.

Student stipend support provided by the Ralph E. Hansmann Science Student Support Fund.