1998 Fiscal Year Final Research Report Summary
Study of apoptosis induction and telomerase activity of carcinomas in digestive tract
| Project/Area Number |
08457324
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tottori University |
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Principal Investigator |
IKEGUCHI Masahide Tottori University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20193188)
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| Co-Investigator(Kenkyū-buntansha) |
MAETA Michio Tottori University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70032208)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Apoptosis / Telomerase activity / Familial adenomatous polyposis / Esophageal cancer |
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| Research Abstract |
We obtained following results between 1996 and 1998.
(1) Human gastric carcinoma cell lines (MKN-28, MKN-45, MKN-74, KATO-III, and HSC-39) were treated with 1 mug/ml cisplatin. Percentages of apoptotic cells were increased more intensively among MKN-45 and MKN-74 cells with a wild-type p53 protein and without bcl-2 protein expression than among HSC-39, MKN-28, and KATO-III cells with a mutation or complete deletion of the gene for p53 and with bcl-2 protein overexpression. The levels of p53 protein increased in MKN-74 cells and the levels of bcl-2 protein were reduced in KATO-III after treatment with cisplatin. Thus, p53 status and the expression of bcl-2 in tumor cells might be good indicators of sensitivity to chemotherapy for patients with gastric cancer.
(2) In 8 patients with familial adenomatous polyposis (FAP), all carcinomas and polyps from 5 patients with carcinomas in their colon and rectum showed high telomerase activity, however, all polyps from 3 patients with no carcinomas
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showed no telomerase activity. Telomerase activity was detected in 75% of control 68 colorectal carcinomas from 68 patients with non-FAP and in 32% of 19 adenomas from 19 patients. The incidence of detectable telomerase activity of adenomas from 11 patients with synchronous colorectal carcinoma (45%) was higher than that of detectable telomerase activity of adenomas from 8 patients without colorectal carcinoma (13%). In FAP, the p53 gene mutations were detected in only 2 carcinomas from 2 patients. These findings suggest that telomerase should be activated before occurrence of p53 gene mutation. In FAP, geneticchanges associated with development of colonic adenoma to carcinoma should occur in hole poiyps of colon and rectum and genetic changes in polyps might activate telomerase activity. The detection of telomerase is a useful marker to decide the time of operation for patients with FAP.
(3) The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomeraseactivity in esophageal carcinomas and normal esophageal tissues adjacent to carcinomas from 52surgically treated patients and normal esophageal epitheliums from 11 noncancerous patientsobtained by biopsy. Telomerase activity was detected in 77% of 52 esophageal carcinomas, in 87% of normal tissue samples adjacent to carcinomas and in 73% of 11 normal esophageal epitheliums from noncancerous patients. hi esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. These results indicate that normal esophageal epitheliums show strong telomerase activity, so, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus. Less
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