Effects of telomerase and intracellular signal transduction pathways on carcinogenesis and development of colorectal carcinoma

Research Project

Project/Area Number	08671442
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Digestive surgery
Research Institution	Tottori University
Principal Investigator	TSUJITANI Shunichi Tottori University Hospital, Assistant Professor, 医学部・附属病院, 講師 (30188544)
Co-Investigator(Kenkyū-buntansha)	YAMAGUCHI Yumi Tottori University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (50273909) KANEKO Tetsuya Tottori University Hospital, Assistant Professor, 医学部・付属病院, 助手 (00243387)
Project Period (FY)	1996 – 1997
Project Status	Completed (Fiscal Year 1997)
Budget Amount *help	¥2,500,000 (Direct Cost: ¥2,500,000) Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000) Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords	Colorectal cancer / Telomere / Telomerase / Genomic instability / Microsatellite / マイクロサテライト / テロメラーゼ活性 / 遺伝子不安定性 / 家族性大腸腺腫症 / 多発癌
Research Abstract	Telomeres of somatic cells are shortening with each cell division. While telomerase which involve the maintenance of telomere length is activated in malignant cells, and as a result, such cells aquire immortality. Mutations in mismatch repair genes result in a mutator phenotype that can be identified by observing microsatellite loci in nonfamilial colorectal cancer as well as hereditary non polyposis colorectal cancer. In this study, we investigated the telomerase activity and the microsatellite instability in nonfamilial colorectal cancers and adenomas. Telomerase activity was detected in 75% of colorectal cancers and in 33% of adenomas. Microsatellite instability was detected in 24% of sporadic cancers, in 54% of multiple cancers, and in 22% of colorectal adenomas. Telomerase activity and microsatellite instability ware independent events in colorectal carcinogenesis. The patients with telomerase activity and microsatellite instability showed poor prognosis. These results indicate that colorectal cancers with both telomerase activity and microsatellite instability may have more malignant potential, and adenomas with both telomerase activity and microsatellite instability may be more intensive precursor of colorectal cancers.