Evidence that MIG-6 is a tumor-suppressor gene
Copyright policy )Evidence that MIG-6 is a tumor-suppressor gene
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.
- Van Andel Institute United States
- Jackson Laboratory United States
- Harvard University United States
- Esperion Therapeutics (United States) United States
- Pfizer (United States) United States
Adenoma, 570, Lung Neoplasms, Epithelial-Cells, Signal-Transduction, Blotting-Northern, Blotting, Western, Gene-Expression-Regulation-Neoplastic, 610, Gallbladder Diseases, Adenocarcinoma, Blotting-Western, Genes-Tumor-Suppressor, Immunoenzyme Techniques, Carcinoma, Non-Small-Cell Lung, Animals, Humans, Carcinoma-Squamous-Cell, Genes, Tumor Suppressor, Carcinoma-Non-Small-Cell-Lung, Receptor-Epidermal-Growth-Factor, Adaptor Proteins, Signal Transducing, Immunoenzyme-Techniques, Hyperplasia, Hepatocyte Growth Factor, Tumor-Cells-Cultured, Epithelial Cells, Mice-Knockout, Blotting, Northern, Bile-Duct-Neoplasms, ErbB Receptors, Gene Expression Regulation, Neoplastic, Bile Duct Neoplasms, Codon, Nonsense, Gallbladder-Diseases, Carcinoma, Squamous Cell, Hepatocyte-Growth-Factor, Mitogen-Activated-Protein-Kinases, Codon-Nonsense, Lung-Neoplasms, Mutation-Missense
Adenoma, 570, Lung Neoplasms, Epithelial-Cells, Signal-Transduction, Blotting-Northern, Blotting, Western, Gene-Expression-Regulation-Neoplastic, 610, Gallbladder Diseases, Adenocarcinoma, Blotting-Western, Genes-Tumor-Suppressor, Immunoenzyme Techniques, Carcinoma, Non-Small-Cell Lung, Animals, Humans, Carcinoma-Squamous-Cell, Genes, Tumor Suppressor, Carcinoma-Non-Small-Cell-Lung, Receptor-Epidermal-Growth-Factor, Adaptor Proteins, Signal Transducing, Immunoenzyme-Techniques, Hyperplasia, Hepatocyte Growth Factor, Tumor-Cells-Cultured, Epithelial Cells, Mice-Knockout, Blotting, Northern, Bile-Duct-Neoplasms, ErbB Receptors, Gene Expression Regulation, Neoplastic, Bile Duct Neoplasms, Codon, Nonsense, Gallbladder-Diseases, Carcinoma, Squamous Cell, Hepatocyte-Growth-Factor, Mitogen-Activated-Protein-Kinases, Codon-Nonsense, Lung-Neoplasms, Mutation-Missense
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