Characterization of peptide aptamers to the Anterior Gradient 2: a novel inhibitor of the tumour suppressor protein p53

Anterior Gradient-2 was identified using proteomic technologies as a protein overexpressed in human cancers. We show here properties of AG2 suggesting it has proto-oncogenic properties:(i) the AG2 protein and gene are unregulated in a tamoxifen resistance panel of breast cancer cells lines, (ii) cell lines overproducing AG2 have an elevated clonogenic activity in vitro and also increase cell growth in a xenograft model, (iii) AG2 protein inhibits the tumour suppressor protein p53, and (iv) AG2 localizes to the endoplasmic reticulum, suggesting a proto-onocogenic signalling pathway exists from endoplasmic reticulum to the nucleus to inhibit p53.

To validate the AG2-mediated endoplasmic reticulum pathway as a possible drug target, we developed peptide aptamers to AG2 protein in order to determine whether the oncogenic properties of the protein can be altered by the peptide ligand.

These studies hold promise for developing new types of drugs that can release and reactivate the tumour suppressor p53 in breast cancers.