Transforming variant of Met receptor confers serum independence and anti-apoptotic property and could be involved in the mouse thymic lymphomagenesis.
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.
Baek
Cheol-Min
CM
Department of Biochemistry, Ajou University Medical School, San 5 Woncheon-dong, Yeongtong-gu, Suwon, 443-721, Korea.
Jeon
Soung-Hoo
SH
Jang
Ja-June
JJ
Lee
Bok Soon
BS
Lee
Jae-Ho
JH
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D050796:STAT3 Transcription Factor; D044967:Serum / Q000378:metabolism; D013950:Thymus Gland; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D017228:Hepatocyte Growth Factor; D004317:Doxorubicin; D019859:Proto-Oncogene Proteins c-met