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Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2
Author(s) -
Hashizume Toshihiro,
Fukuda Takayuki,
Nagaoka Tadahiro,
Tada Hiroko,
Yamada Hidenori,
Watanabe Kazuhide,
Salomon David S.,
Seno Masaharu
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2008.03.012
Subject(s) - internalization , endocytosis , endocytic cycle , endosome , microbiology and biotechnology , clathrin , skbr3 , tyrosine kinase , downregulation and upregulation , erbb3 , epidermal growth factor , biology , transferrin receptor , epidermal growth factor receptor , receptor , erbb , receptor tyrosine kinase , chemistry , kinase , signal transduction , biochemistry , cancer cell , intracellular , gene , cancer , genetics , human breast
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.