The mature secreted form of amphiregulin is an 84-amino acid residue glycosylated polypeptide which is generated by proteolytic processing of a 252-amino acid transmembrane precursor. Seven different polypeptide ligands, which derive from distinct genes, are capable of binding to the extracellular domain of EGFR; these are EGF, TGFa, AR, HB-EGF, cripto-1, epiregulin, and betacellulin. All of these growth factors contain a characteristic EGF-like domain which is defined by 6 evenly spaced cysteine residues that generate 3 loops through the formation of disulfide bonds. Amphiregulin expression is induced by phorbol ester, estrogen, androgen, and other EGFR ligands. In vitro, amphiregulin functions as an autocrine growth stimulator to drive proliferation of colon carcinoma cells, normal and oncogene-transformed mammary epithelial cells, cervical carcinoma cells, prostate cancer cells, and keratinocytes. Amphiregulin is important in the development of human placenta and murine mammary gland. It is reportedly overexpressed in human cancers of breast, colon, stomach and pancreas.

Cell Membrane