| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
1. Histone acetylation status in gastrointestinal carcinomas
Reduced expression of acetylated histone H4 (low acetylation status) was detected in 66% of gastric cancers, 46% of gastric adenomas, 78% of colorectal cancers, and 30% of colorectal adenomas, respectively. Histone deacetylase inhibitor (trichostatin A : TSA) inhibited cell growth and induced apoptosis in gastric cancer cell lines, while TSA induced the expression of p21, CBP, BAK and cyclin E.Introduction of demethylase (MBD2) into gastric cancer cell line or TSA treatment retrieved the expression of CD44 and p16, while HDAC1 expression was suppressed. Interaction between histone acetylation and DNA methylation may be involved in gastrointestinal carcinogenesis through modulation of gene expression related to proliferation and apoptosis.
2. Telomerase and telomere DNA interacting molecules in gastrointestinal carcinomas
Strong telomerase activity and increased TERT expression were detected in most of the gastrointestinal carcin
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omas. 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. Increased expression of TRF1, TRF2 and tankyrase was detected in 50-60% of gastric carcinomas. The expression of TIN2 and hRAP1 was increased in 30% and 65% of gastric carcinomas, respectively. MRE11 complex consists of MRE11, RAD50 and NBS1 which acts as DNA repair enzyme. Increased expression of MRE11 RAD50 and NBS1 was found in 65%, 70% and 80% of gastric carcinomas, respectively.
3. Relationship between histone acetylation and telomerase in gastrointestinal carcinomas
Majorities of gastrointestinal carcinomas and a portion of precancerous lesions revealed low levels of histone acetylation and strong telomerase activity with increased TERT expression, suggesting that their interaction may deeply participate in gastrointestinal carcinogenesis at early stage. Less
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