Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human colorectal cancers.
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-x(L)and 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-x(L)genes 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-x(L)mRNA 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-x(L)was not affected by treatment with c-met-antisense oligonucleotides. These findings suggest that Met expression modulates apoptosis through bcl -w expression in colorectal tumours.
Kitamura
S
S
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kondo
S
S
Shinomura
Y
Y
Kanayama
S
S
Miyazaki
Y
Y
Kiyohara
T
T
Hiraoka
S
S
Matsuzawa
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism; D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004247:DNA / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C491073:BCL2L2 protein, human; D016895:Culture Media, Serum-Free; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D011506:Proteins; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D004247:DNA; D019859:Proto-Oncogene Proteins c-met