Faculty Collaboration Database

Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer 2008 Dec;47(12):1025-37

Date

08/19/2008

Pubmed ID

18709663

Pubmed Central ID

PMC2583960

DOI

10.1002/gcc.20604

Scopus ID

2-s2.0-57149092131 (requires institutional sign-in at Scopus site)   288 Citations

Abstract

MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker.

Author List

Ma PC, Tretiakova MS, MacKinnon AC, Ramnath N, Johnson C, Dietrich S, Seiwert T, Christensen JG, Jagadeeswaran R, Krausz T, Vokes EE, Husain AN, Salgia R

MESH terms used to index this publication - Major topics in bold

Gene Expression
Humans
Lung Neoplasms
Mutation
Neoplasms
Neovascularization, Pathologic
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-met
Receptors, Growth Factor
Stem Cells
Tumor Cells, Cultured