Characterization of a novel amphiregulin-related molecule in 12-O-tetradecanoylphorbol-13-acetate-treated breast cancer cells

Journal of Cellular Physiology
I Martínez-LacaciR B Dickson

Abstract

Amphiregulin (AR) can be induced at the mRNA level by 17-beta-estradiol (E2) or the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study compares the effects of TPA and E2 on the regulation of processing of AR isoforms and on subcellular localization in human MCF-7 breast cancer cells. AR was localized in the nucleus of MCF-7 cells after E2 treatment, whereas it was predominantly secreted after TPA treatment. AR isoforms of 28, 18, and 10 kDa and an additional species of approximately 55-60 kDa were detected in the cellular conditioned media after TPA stimulation. Expression of this unusual AR isoform was inhibited by protein kinase C (PKC) inhibitors such as bryostatin or H-7. The biochemical properties of this isoform are consistent with it being an N-linked glycosylated form of the AR precursor that contains unprocessed mannose residues. The size of this large isoform is reduced to approximately 40 kDa after treating the TPA-induced MCF-7 cells with tunicamycin or treating the conditioned media of such cells with N-glycosidase F or with endoglycosidase H. Moreover, this isoform is able to blind several lectins with specificity for mannose residues. The 55-60 kDa glycosylated AR isoform, like lo...Continue Reading

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Citations

Apr 26, 2008·Journal of Mammary Gland Biology and Neoplasia·Nicole E Willmarth, Stephen P Ethier
Dec 28, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Neal A EnglertDavid C Spink
Jul 15, 2004·International Journal of Cancer. Journal International Du Cancer·Sylvie DesruisseauYolande Berthois
Sep 17, 2011·Journal of Proteomics·Elena Bonzon-KulichenkoJesús Vázquez
Jan 2, 2008·Journal of Proteome Research·Jon M JacobsBrian D Thrall

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