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Evidence that MIG-6 is a tumor-suppressor gene
1Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, MI 49503, USA. yu-wen.zhang@vai.org
Oncogene
|July 5, 2006
Summary
Mitogen-inducible gene 6 (MIG-6) acts as a tumor suppressor, regulating growth factor signaling. Loss of MIG-6 function, through mutation or silencing, contributes to lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The 1p36 chromosomal region is frequently altered in human lung cancer.
- Mitogen-inducible gene 6 (MIG-6) negatively regulates epidermal growth factor (EGF) signaling.
- EGF receptor (EGFR) and Met signaling pathways are often co-activated in lung cancer.
Purpose of the Study:
- To investigate the role of MIG-6 in lung cancer.
- To determine if MIG-6 functions as a tumor suppressor.
- To identify mechanisms of MIG-6 inactivation in lung tumors.
Main Methods:
- Analysis of MIG-6 expression and mutations in human lung cancer cell lines.
- Investigating MIG-6 induction by EGF and hepatocyte growth factor/scatter factor (HGF/SF).
- Germline disruption of the Mig-6 gene in mice to assess tumor development.
Main Results:
- MIG-6 is induced by EGF and HGF/SF in a mitogen-activated protein kinase-dependent manner.
- Human lung cancer cell lines lacking MIG-6 induction harbor coding mutations or transcriptional silencing of MIG-6.
- Germline deletion of Mig-6 in mice results in spontaneous epithelial tumors, including lung adenocarcinoma.
Conclusions:
- MIG-6 functions as a tumor suppressor gene.
- Inactivation of MIG-6 contributes to lung tumorigenesis.
- MIG-6 is a candidate gene for the 1p36 alterations observed in lung cancer.
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