Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2

Toshihiro Hashizume, Takayuki Fukuda, Tadahiro Nagaoka, Hiroko Tada, Hidenori Yamada, Kazuhide Watanabe, David S. Salomon, Masaharu Seno

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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.

Original languageEnglish
Pages (from-to)814-826
Number of pages13
JournalCell Biology International
Issue number7
Publication statusPublished - 01-07-2008


All Science Journal Classification (ASJC) codes

  • Cell Biology

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