title: Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7.
abstract: A glycoprotein, termed amphiregulin (AR), inhibits growth of several human carcinoma cells in culture and stimulates proliferation of human fibroblasts and certain other tumor cells. It has been purified to apparent homogeneity from serum-free conditioned medium of MCF-7 human breast carcinoma cells that had been treated with phorbol 12-myristate 13-acetate. AR is a single-chain extremely hydrophilic glycoprotein containing cysteines in disulfide linkage(s) that are essential for biological activity; it is stable between pH 2 and pH 12 and after heating for 30 min at 56 degrees C but unstable at 100 degrees C. The apparent molecular weights of AR and N-Glycanase-treated AR are 14,000 and 15,000, respectively, as assessed by gel chromatography, and approximately 22,500 and approximately 14,000, respectively, as determined by polyacrylamide gel electrophoresis. Treatment of AR with N-Glycanase, O-Glycanase, or neuraminidase does not affect its activity. The pI of AR is approximately 7.8. The amino-terminal amino acid sequence of AR has been determined, and no significant sequence homology between AR and other proteins was found. The molecule thus appears to be a distinct growth regulatory protein.
authors.affiliation: Oncogen, Seattle, WA 98121.
authors.forename: M
authors.initials: M
authors.lastname: Shoyab
authors.forename: V L
authors.initials: VL
authors.lastname: McDonald
authors.forename: J G
authors.initials: JG
authors.lastname: Bradley
authors.forename: G J
authors.initials: GJ
authors.lastname: Todaro
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000595:Amino Acid Sequence; D066258:Amphiregulin; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D006133:Growth Substances / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D013755:Tetradecanoylphorbol Acetate