Exp Mol Med.
2004 Aug;36(4):283-291.
Transforming variant of Met receptor confers serum independence and anti-apoptotic property and could be involved in the mouse thymic lymphomagenesis
- Affiliations
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- 1Department of Biochemistry Ajou University Medical School San 5 Woncheon-dong, Yeongtong-gu, Suwon 443-721, Korea.
- 2Chronic Inflammatory Disease Research Center Ajou University Medical School San 5 Woncheon-dong, Yeongtong-gu Suwon 443-721, Korea.
- 3Department of Pathology Seoul National University College of Medicine, Seoul 110-799, Korea.
- 4Department of Biotechnology, College of Engineering, Yonsei University, Seoul 120-749, Korea. jhlee64@ajou.ac.kr
Abstract
- Met tyrosine kinase receptor, the receptor of hepatocyte growth factor/scatter factor (HGF/SF), is present in mouse tissues as two major isoforms differing by a 47-aminoacid segment in the juxtamembrane domain via alternative splicing of exon 14. We found that the smaller isoform of Met (Sm-Met) was highly transformable in both in vitro and in vivo tumorigenesis assays. In this report, close examination of the transforming activity of the Sm-Met showed that the expression of Sm-Met conferred the cells serum independence and anti- apoptotic property when treated with doxorubicin. These properties of Sm-Met seemed to be originated from its far longer maintenance of tyrosine kinase activity after the binding of HGF/SF. Interestingly, the longer maintenance of activated status was accompanied with more increase of tyrosine phosphorylation of Stat3 protein. Moreover, we have tried to find (an) animal tumorigenesis model(s) showing the increase in the expression of this transforming variant of Met. In gamma-ray-induced mouse thymic lymphoma model, the expression of the mRNAs for Sm-Met was significantly increased as well as those of wild type Met and HGF/SF, suggesting a possible role of the Sm-Met in tumorigenesis in vivo.
Keyword
MeSH Terms
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Animals
*Apoptosis
Cell Proliferation
Cell Survival
*Cell Transformation, Neoplastic
DNA-Binding Proteins/metabolism
Doxorubicin/pharmacology
Hepatocyte Growth Factor/pharmacology
Lymphoma/*etiology/genetics/metabolism
Mice
NIH 3T3 Cells
Phosphorylation
Protein Isoforms/genetics/metabolism
Proto-Oncogene Protein c-met/genetics/*metabolism
RNA, Messenger/analysis/metabolism
Research Support, Non-U.S. Gov't
Serum/metabolism
Thymus Gland
Trans-Activators/metabolism
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