TY - JOUR
T1 - Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2
AU - Hashizume, Toshihiro
AU - Fukuda, Takayuki
AU - Nagaoka, Tadahiro
AU - Tada, Hiroko
AU - Yamada, Hidenori
AU - Watanabe, Kazuhide
AU - Salomon, David S.
AU - Seno, Masaharu
N1 - Funding Information:
We thank Ms. N. Hironaka for the construction of the sErbB2 expression plasmid. We thank Ms. H. Sato for real-time quantitative PCR work. This research was supported by the Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research.
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cellbi.2008.03.012
DO - 10.1016/j.cellbi.2008.03.012
M3 - Article
C2 - 18442934
AN - SCOPUS:44549087930
SN - 1065-6995
VL - 32
SP - 814
EP - 826
JO - Cell Biology International
JF - Cell Biology International
IS - 7
ER -
