Evidence that MIG-6 is a tumor-suppressor gene.
Document Type
Article
Publication Date
2007
Keywords
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
First Page
269
Last Page
276
JAX Source
Oncogene 2007 Jan; 26(2):269-76.
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.
Recommended Citation
Zhang YW,
Staal B,
Su Y,
Swiatek P,
Zhao P,
Cao B,
Resau J,
Sigler R,
Bronson R,
Vande WG.
Evidence that MIG-6 is a tumor-suppressor gene. Oncogene 2007 Jan; 26(2):269-76.