targeting of both the c-met and egfr pathways results in additive inhibition of lung tumorigenesis in transgenic mice针对c-met和egfr通路导致添加剂抑制转基因小鼠的肺肿瘤发生.pdf

Cancers 2010, 2, 2153-2170; doi:10.3390/cancers2042153 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Article Targeting of Both the c-Met and EGFR Pathways Results in Additive Inhibition of Lung Tumorigenesis in Transgenic Mice Laura P. Stabile 1,6, Mary E. Rothstein 1 , Phouthone Keohavong 2,6, Diana Lenzner 3, Stephanie R. Land 3,6, Autumn L. Gaither-Davis 1,6, K. Jin Kim 4, Naftali Kaminski 5,6 and Jill M. Siegfried 1,6,* 1 Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA; E-Mails: las22@ (L.P.S.); meb63@ (M.E.R); gaitherdavisa@ (A.L.G.D) 2 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; E-Mail: pho1@ 3 Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15213, USA; E-Mails: del9@ (D.L.); Land@ (S.R.L) 4 Galaxy Biotech, LLC, Sunnyvale, CA 94089, USA; E-Mail: jin.kim@ 5 Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA; E-Mail: nak38@ 6 Lung and Thoracic Malignancy Program, University of Pittsburgh, Pittsburgh, PA 15213, USA * Author to whom correspondence should be addressed; E-Mail: siegfriedjm@; Tel.: +1-412-623-7769; Fax: +1-412-623-7768. Received: 20 October 2010; in revised form: 25 November 2010 / Accepted: 21 December 2010 / Published: 22 December 2010 Abstract: EGFR and c-Met are both overexpressed in lung cancer and initiate similar downstream signaling, which may be redundant. To determine how frequently ligands that initiate signaling of both pathways are found in lung cancer, we analyz