z-logo
Premium
EGFR tyrosine kinase activity is not necessary for ligand‐induced EGFR down‐regulation in ovarian cancer cells
Author(s) -
Cao Cong,
Ji Chao,
Amaral Ashley,
LeeCouture Avery,
Kouttab Nicola,
Chu Wenming,
Di Wen,
Wan Yinsheng
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.21.5.a248-c
Subject(s) - grb2 , cancer research , tyrosine kinase , receptor tyrosine kinase , epidermal growth factor receptor , erbb3 , signal transduction , cyclin dependent kinase 8 , tyrosine kinase inhibitor , chemistry , neuregulin , egfr inhibitors , proto oncogene tyrosine protein kinase src , ror1 , microbiology and biotechnology , pi3k/akt/mtor pathway , biology , cancer , platelet derived growth factor receptor , medicine , receptor , growth factor , biochemistry , notch signaling pathway
Overexpression of EGFR is associated with advanced‐stage disease and poor prognosis of ovarian cancer, and activation of EGFR signaling pathway is involved in increased cell proliferation, angiogenesis, metastasis, and decreased apoptosis. Tyrosine kinase activity is essential for signal transduction and for receptor down‐regulation. However, we found in this study that tyrosine kinase activity is not necessary in ligand‐induced EGFR down‐regulation in Caov3 cells. EGFR tyrosine kinase inhibitors, such as PD153035, AG1478, as well as non‐specific tyrosine kinase inhibitor PP2 did not reverse EGF‐induced down‐regulation of EGFR. These findings permit us to develop the following exciting but unconventional strategy, namely, priming ovarian cancer cell with EGF together with EGFR inhibitor PD153035. This priming down‐regulates EGFR without induction of mitogenic signals. EGF plus EGFR inhibitor‐primed ovarian cancer cells displayed more sensitive to Taxol‐induced cell death and resistant to EGF‐induced cell migration, cell proliferation as well as ERK, PI3K activation. Mechanistic analysis indicated that PD153035, which did not reverse ligand‐induced EGFR down‐regulation, blocked EGF‐induced EGFR activation as well as EGFR binding with c‐cbl and Grb2. Taken together, we contend that combination of EGF priming with EGFR inhibitors would ultimately result in better chemotherapeutical outcome.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here