|Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
1. Genetic and chromosomal instabilities in gastrointestinal carcinomas
Genetic instability (replication error : PER) was examined in the gastric carcinomas by microsatellite analysis, and was found in 30% of the cases. Especially, the instability at D 17S855 locus (near BRCA1) was frequent in younger patients. RER was also detected in a part of intestinal metaplasia next to gastric carcinoma. RER at more than two of the four loci was found in 3% of the gastric carcinomas, a half of which had multiple primary cancers.
Strong telomerase activity and increased hTR expression were detected in most of the gastric carcinomas and a portion of precancerous lesions. The telomerase activities were well correlated with the levels of TERT expression in most of the gastric and colorectal carcinomas. TERT expression was also detected in some of the adenomas and intestinal metaplasia of the stomach.
2. Genetic abnormalities of cell cycle regulators in gastrointestinal carcinomas
Gene amplification and o
verexpression of cyclin E occurred frequently in the gastric and colorectal carcinomas that was closely related with high grade malignancy. About 70% of the gastric carcinomas expressed CDC25B at high levels. Reduced expression of p27, a CDK inhibitor, correlated well with aggressive behavior (advanced tumor stage, deeply invasion, and lymph-node metastasis) of the gastric and colorectal carcinomas. Gene amplification of E2F-1, an important target molecule of cell cycle regulators, was detected in 4% and 25% of the gastric and colorectal carcinomas, respectively. About 40% of the gastric carcinomas overexpressed E2F-1 mRNA.On the other hand, the expression of E2F-3 was reduced in 70% of the gastric carcinomas.
3. Relationship between telomerase and cell cycle regulators
Relationship between telomerase activity and the expression of various cyclins and CDK inhibitors in the gastric carcinomas. The expression of cyclin E tended to correlate with the telomerase activity, while no obvious tendency was detected between telomerase and the expression of p21 and p27. Less