Evidence that MIG-6 is a tumor-suppressor gene.

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Adenocarcinoma, Adenoma, Animals, Bile-Duct-Neoplasms, Blotting-Northern, Blotting-Western, Carcinoma-Non-Small-Cell-Lung, Carcinoma-Squamous-Cell, Codon-Nonsense, Epithelial-Cells, Gallbladder-Diseases, Gene-Expression-Regulation-Neoplastic, Genes-Tumor-Suppressor, Hepatocyte-Growth-Factor, Humans, Hyperplasia, Immunoenzyme-Techniques, Lung-Neoplasms, Mice-Knockout, Mitogen-Activated-Protein-Kinases, Mutation-Missense, Receptor-Epidermal-Growth-Factor, Signal-Transduction, Tumor-Cells-Cultured

JAX Source

Oncogene 2007 Jan; 26(2):269-76.


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.