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Cancer Research 67, 2081, March 1, 2007. doi: 10.1158/0008-5472.CAN-06-3495
© 2007 American Association for Cancer Research
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Cell, Tumor, and Stem Cell Biology

Lung Cancer Cell Lines Harboring MET Gene Amplification Are Dependent on Met for Growth and Survival

Bart Lutterbach, Qinwen Zeng, Lenora J. Davis, Harold Hatch, Gaozhen Hang, Nancy E. Kohl, Jackson B. Gibbs and Bo-Sheng Pan

Cancer Biology and Therapeutics, Merck Research Laboratories, Boston, Massachusetts

Requests for reprints: Bart Lutterbach, Department of Molecular Oncology, BMB 9-122, Merck Research Laboratories, 33 Avenue, Louis Pasteur, Boston, MA 02115. Phone: 617-992-2038; E-mail: bart_lutterbach{at}merck.com.

Recent clinical successes of small-molecule epidermal growth factor receptor (EGFR) inhibitors in treating advanced non–small cell lung cancer (NSCLC) have raised hopes that the identification of other deregulated growth factor pathways in NSCLC will lead to new therapeutic options for NSCLC. Met, the receptor for hepatocyte growth factor, has been implicated in growth, invasion, and metastasis of many tumors including NSCLC. To assess the functional role for Met in NSCLC, we evaluated a panel of nine lung cancer cell lines for Met gene amplification, Met expression, Met pathway activation, and the sensitivity of the cell lines to short hairpin RNA (shRNA)–mediated Met knockdown. Two cell lines, EBC-1 and H1993, showed significant Met gene amplification and overexpressed Met receptors which were constitutively phosphorylated. The other seven lines did not exhibit Met amplification and expressed much lower levels of Met, which was phosphorylated only on addition of hepatocyte growth factor. We also found a strong up-regulation of tyrosine phosphorylation in ß-catenin and p120/{delta}-catenin in the Met-amplified EBC-1 and H1993 cell lines. ShRNA-mediated Met knockdown induced significant growth inhibition, G1-S arrest, and apoptosis in EBC-1 and H1993 cells, whereas it had little or no effect on the cell lines that do not have Met amplification. These results strongly suggest that Met amplification identifies a subset of NSCLC likely to respond to new molecular therapies targeting Met. [Cancer Res 2007;67(5):2081–8]




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Correction: Met Dependence of Lung Cancer Cell Lines
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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 2007 by the American Association for Cancer Research.