title: Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2.
abstract: ErbB2, which is a member of the epidermal growth factor (erbB) receptor family, is frequently overexpressed in breast and ovarian cancers. Antibody and small molecule anti-tyrosine kinase inhibitors have been developed for targeted therapies for cancers overexpressing erbB2. Internalization and downregulation of erbB2, which is induced by a ligand, may be important for efficacious therapeutic effects. However, ligand-dependent erbB2 internalization has not been well characterized. Here we investigated the internalization of erbB2 in SKBr3 and SKOv3 cells, both overexpressing erbB2, using an EC-1 peptide fused to eGFP (EC-eGFP), which specifically binds to erbB2. ErbB2 was internalized in SKOv3 cells when the cells were treated with EC-eGFP. The accumulation of endosomal erbB2 was EC-eGFP dependent, which colocalized with transferrin implying endocytosis via clathrin-coated pits. In contrast, internalization of erbB2 was not observed in SKBr3 cells. As a result, two different mechanisms, which are cell type dependent for the internalization of erbB2, are proposed.
authors.affiliation: Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashizume
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuda
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tada
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Watanabe
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008024:Ligands; D010456:Peptides, Cyclic / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D014168:Transferrin