Abstract
The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor. In the present study, we investigated the role of met expression on the modulation of apoptosis in colorectal tumours. The gene expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl-xLand bcl-w, were analysed in human colorectal adenomas and adenocarcinomas by using a quantitative polymerase chain-reaction combined with reverse transcription. In seven of 12 adenomas and seven of 11 carcinomas, the c-met gene was overexpressed. The bcl-w, bcl-2 and bcl-xLgenes were over-expressed in nine, five and six of 12 adenomas and in five, two and seven of 11 carcinomas, respectively. The c-met mRNA level in human colorectal adenomas and carcinomas was correlated with bcl-w but not with bcl-2 or with bcl-xLmRNA level. The administration of c-met-antisense oligonucleotides decreased Met protein levels in the LoVo human colon cancer cell line. In the case of c-met -antisense-treated cells, apoptotic cell death induced by serum deprivation was more prominent, compared to control or c-met-nonsense-treated cells. Treatment with c-met- antisense oligonucleotides inhibits the gene expression of bcl-w in LoVo cells. On the other hand, the gene expression of bcl-2 or bcl-xLwas not affected by treatment with c-met-antisense oligonucleotides. These findings suggest that Met expression modulates apoptosis through bcl-w expression in colorectal tumours. © 2000 Cancer Research Campaign
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Kitamura, S., Kondo, S., Shinomura, Y. et al. Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human colorectal cancers. Br J Cancer 83, 668–673 (2000). https://doi.org/10.1054/bjoc.2000.1301
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DOI: https://doi.org/10.1054/bjoc.2000.1301
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