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  • Original Article
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Evidence that MIG-6 is a tumor-suppressor gene

Oncogene volume 26, pages 269–276 (2007)Cite this article

Abstract

Mitogen-inducible gene 6 (MIG-6) is located in human chromosome 1p36, a locus frequently associated with human lung cancer. MIG-6 is a negative regulator of epidermal growth factor (EGF) signaling, and we show that Mig-6 – like EGF – is induced by hepatocyte growth factor/scatter factor (HGF/SF) in human lung cancer cell lines. Frequently, the receptors for both factors, EGFR and Met, are expressed in same lung cancer cell line, and MIG-6 is induced by both factors in a mitogen-activated protein kinase-dependent fashion. However, not all tumor lines express MIG-6 in response to either EGF or HGF/SF. In these cases, we find missense and nonsense mutations in the MIG-6 coding region, as well as evidence for MIG-6 transcriptional silencing. Moreover, germline disruption of Mig-6 in mice leads to the development of animals with epithelial hyperplasia, adenoma, and adenocarcinoma in organs like the lung, gallbladder, and bile duct. These data suggests that MIG-6 is a tumor-suppressor gene and is therefore a candidate gene for the frequent 1p36 genetic alterations found in lung cancer.

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Acknowledgements

We thank Bryn Eagleson, Jason Martin, and Kellie Sisson for helping with the mice, Matt VanBrocklin and Han-Mo Koo for providing the lung cancer cell lines, Bree Berghuis and JC Goolsby for histological assistance, David Petillo for sequencing, Eric Kort for statistic analysis, David Nadziejka for technical editing of the manuscript, and Michelle Reed and Troy Carrigan for manuscript preparation. This work was supported by the Van Andel Foundation and in part by the Michigan Economic Development Corporation and Michigan Technology Tri-Corridor Grant MAMC 085P1000815.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, MI, USA

    Y-W Zhang, B Staal, Y Su & G F Vande Woude

  2. Laboratory of Germline Modification, Van Andel Research Institute, Grand Rapids, MI, USA

    P Swiatek

  3. Laboratory of Antibody Technology, Van Andel Research Institute, Grand Rapids, MI, USA

    P Zhao & B Cao

  4. Laboratory of Analytical, Cellular, and Molecular Microscopy, Van Andel Research Institute, Grand Rapids, MI, USA

    J Resau

  5. Division of Pfizer, Esperion Therapeutics, Ann Arbor, MI, USA

    R Sigler

  6. Department of Pathology, Harvard Medical School, Boston, MA, USA

    R Bronson

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  1. Y-W Zhang
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Correspondence to Y-W Zhang.

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Zhang, YW., Staal, B., Su, Y. et al. Evidence that MIG-6 is a tumor-suppressor gene. Oncogene 26, 269–276 (2007). https://doi.org/10.1038/sj.onc.1209790

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