Title of article :
Src inhibitor dasatinib inhibits growth of breast cancer cells by modulating EGFR signaling
Author/Authors :
Nautiyal، نويسنده , , Jyoti and Majumder، نويسنده , , Pralay and Patel، نويسنده , , Bhaumik B. and Lee، نويسنده , , Francis Y. and Majumdar، نويسنده , , Adhip P.N، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2009
Pages :
9
From page :
143
To page :
151
Abstract :
EGF-receptor family members (EGFRs) as well as c-Src are over expressed in ∼70% of breast cancer, and in most of the tumors c-Src is co-over expressed with at least one of the EGFRs, suggesting that they may interact functionally and play a role in the development and progression of the malignancy. We hypothesize that a small molecule inhibitor of c-Src dasatinib (BMS-354825; Bristol Myers Squibb), exerts its effects on breast cancer cells by modulating EGFR signaling. Indeed, we found that dasatinib causes inhibition of breast cancer cells overexpressing EGFR, HER-2 and HER-3 (MDA-MB-468, SKBR3, MDA-MB-453, and MDA-MB-231) in a dose and time-dependent manner. Dasatinib also stimulated apoptosis in MDA-MB-468 cells, which could be attributed to activation of both caspase-9 and -8 and arrest of the cell cycle at G0/G1 cycle. Furthermore, dasatinib markedly inhibited colony formation, cell invasion, migration and angiogenesis, accompanied by decreased phosphorylation of EGFR and c-Src and their downstream effector molecules Akt and Erks. Our data suggest that dasatinib mediates its action in part through EGFR signaling and could be a potential therapeutic agent for breast cancer.
Keywords :
EGFR , c-src , Metastatic potential , Cell survival and proliferation , Triple-negative breast cancer
Journal title :
Cancer Letters
Serial Year :
2009
Journal title :
Cancer Letters
Record number :
1817704
Link To Document :
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