Amphiregulin (AR) binds to EGF-Receptor (EGFR) with lower affinity than EGF. The mature secreted form AR is an 84-amino acid residue glycosylated polypeptide growth regulator, 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 ligands include EGF, TGFalpha, AR, HB-EGF, cripto-1, epiregulin, and beta cellulin. All of these growth factors contain a characteristic EGF-like domain which is defined by six evenly spaced cysteine residues that generate three loops through the formation of disulfide bonds. AR protein has been localized by immunohistochemistry to the epithelium of the colon, stomach, pancreas, breast, and placenta. AR is reportedly overexpressed in human cancers of breast, colon, stomach, and pancreas.