| Literature DB >> 23680147 |
Bijay S Jaiswal1, Noelyn M Kljavin, Eric W Stawiski, Emily Chan, Chaitali Parikh, Steffen Durinck, Subhra Chaudhuri, Kanan Pujara, Joseph Guillory, Kyle A Edgar, Vasantharajan Janakiraman, Rolf-Peter Scholz, Krista K Bowman, Maria Lorenzo, Hong Li, Jiansheng Wu, Wenlin Yuan, Brock A Peters, Zhengyan Kan, Jeremy Stinson, Michelle Mak, Zora Modrusan, Charles Eigenbrot, Ron Firestein, Howard M Stern, Krishnaraj Rajalingam, Gabriele Schaefer, Mark A Merchant, Mark X Sliwkowski, Frederic J de Sauvage, Somasekar Seshagiri.
Abstract
The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression in vivo.Entities:
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Year: 2013 PMID： 23680147 DOI： 10.1016/j.ccr.2013.04.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743