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Down‐regulation pathways of insulin‐like growth factor I receptor induced by anti‐IGFIR antibodies
Author(s) -
FujitaYamaguchi Yoko,
Ohtani Masahiro,
Numasaki Maki,
Yajima Yukiko
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1191-c
Subject(s) - receptor , antibody , monoclonal antibody , chemistry , signal transduction , cell growth , biology , microbiology and biotechnology , biochemistry , immunology
The insulin‐like growth factor I receptor (IGFIR) plays a critical role in cell proliferation and survival. We previously reported that a recombinant anti‐IGFIR antibody, scFv‐Fc, consisting of 1H7 monoclonal antibody (mAb)‐derived single chain antibody (scFv) and human IgG Fc, significantly suppressed breast tumor growth, and proposed IGFIR down‐regulation as a mechanism for tumor growth inhibition (Horm Metab Res. 35, 2003, Cancer Res. 63, 2003). In this study, effects of various anti‐IGFIR mAbs on IGFIR down‐regulation and signaling pathways in MCF‐7 breast cancer cells were examined by Western blotting. All five mAbs used, despite showing different effects on IGFIR signaling, down‐regulated IGFIR. Pretreatment of MCF‐7 cells with methylamine substantially reduced the antibody‐mediated IGFIR down‐regulation whereas MG115 did not. These results suggest that anti‐IGFIR antibodies with different epitope‐specificities can cause IGFIR down‐regulation via a lysosome‐dependent pathway in an IGFIR activation‐independent manner. Further analyses including immunofluorescence and confocal microscory on the down‐regulation and degradation of IGFIR caused by antibodies are in progress.