Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human colorectal cancers

• Published in: British journal of cancer Vol. 83; no. 5; pp. 668 - 673
• Main Authors: KITAMURA, S, KONDO, S, SHINOMURA, Y, KANAYAMA, S, MIYAZAKI, Y, KIYOHARA, T, HIRAOKA, S, MATSUZAWA, Y
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.09.2000
• Subjects: Adenocarcinoma - metabolism; Adenoma - metabolism; Adult; Aged; Apoptosis; Apoptosis Regulatory Proteins; bcl-w gene; bcl-X Protein; Biological and medical sciences; Blotting, Western; Cancer research; Carcinoma - metabolism; Case-Control Studies; Colon - metabolism; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Culture Media, Serum-Free; DNA - metabolism; Female; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Growth factors; Humans; Kinases; Male; Medical research; Medical sciences; Met gene; Middle Aged; Mucous Membrane - metabolism; Oligonucleotides, Antisense - metabolism; Other treatments; Polymerase chain reaction; Protein Biosynthesis; Proteins; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-met - metabolism; Regular; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Time Factors; Treatment. General aspects; Tumor Cells, Cultured; Tumors; Up-Regulation; United States > US; Human; Cell culture; Rectal disease; Hepatocyte growth factor; Case control study; Malignant tumor; Experimental study; Gene expression; Antisense oligonucleotide; Colonic disease; Membrane receptor; Rectum; Digestive diseases; Intestinal disease; Physiology; Colon; Gene therapy; Protooncogene; Apoptosis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.2000.1301

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.