|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1995 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥1,100,000 (Direct Cost : ¥1,100,000)
The expression of 6.0 Kb c-met abnormal transcript was proven to be closely correlated with progression and metastasis of gastric cancer. The aim of this grant aided research termed between 1993 and 1995 was to clone this c-met abnormal transcript and clarify the nature of c-met transcripts in neoplastic and non-neoplastic gastric tissue. The results and estimations of the research are summarized as following :
1. The attempt for the molecular cloning of 6.0 Kb c-metabnormal transcript was conducted with (1) cDNA library from gastric cancer cell line KATO-III, (2) high molecular weight pAP3 neo cDNA library from MKN-28 stomach cancer cell line and (3) genomic DNA library from normal human peripheral white blood cell using pmetH probe. Although several positive clones were obtained from each library system, the full length 6.0 Kb abnormal transcript could not be available. The cause of the cloning failure was considered to be due to the large size as well as the rarity of the target transcript. Some highly sensitive like lonk RT-PCR cloning may improve the cloning efficiency.
2. Fragments of c-met cDNA were analyzed by RT-PCR method. Gastric cancer tissue as well as corresponding normal gastric mucosa was found to express a splice variant lacking nt 2265 to nt 2319 of c-metcDNA preferentially (Yokozaki, H., et al., Oncology Reports, 3,1996 (in press) ).
3. Loss of heterozygosity (LOH) on the long arm of the chromosome 7 including c-met locus in human gastric carcinoma tissues was analyzed extensively. Cases with LOH at D7S95 showed significantly worse prognosis than those without the LOH.This finding suggested that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.