2001 Fiscal Year Final Research Report Summary
Regulatory mechanism of the expression of TERT mRNA and telomerase activity in oral cancer
| Project/Area Number |
12671981
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
OZEKI Satoru Fukuoka Dental College, Oral and Maxillofacial Surgery, Professor, 歯学部, 教授 (80117077)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Masayoshi Fukuoka Dental College, Oral and Maxillofacial Surgery, Assistant, 歯学部, 助手 (40320337)
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| Project Period (FY) |
2000 – 2001
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| Keywords | tongue cancer / telomerase / carcinogenesis / 4-NQO / human telomerase RNA (hTR) / hTEP1 / hTERT / human telomerase catalytic subunit |
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| Research Abstract |
Telomeres are considered one factor governing the life span of cells. In most immortalized cells or cancer calls, telomerase activity, which is one of the mechanisms responsible for elongation of shortened telomeres, is increased. Telomerase activity is therefore considered to play a crucial role in carcinogenesis. To study the role of telomerase activity in carcinogenesis in vivo, we investigated the relation between telomerase activity and histopathological findings of the tongue after treatment of DA rats with the carcinogen 4-NQO. Normal epithelium or epithelial hyperplasia of the tongue was found to have weak but detectable telomerase activity. Telomerase activity was considerably upregulated very early after the onset of malignant changes. Our results showed that telomerase was upregulated during early carcinogenesis of the tongue. This upregulation of telomerase activity may contribute to in vivo carcinogenesis. Telomerase activation is thought to be crucial for the sustained growth or progression of most cancer cells and its activation is an important step in carcinogenesis. Recently, three major subunits of human telomerase, hTR, hTEP1 and hTERT have been identified. In current study, we quantified the expression of these telomerase subunits mRNA in oral tissues with a RT-PCR method and evaluated the correlation between their expression and telomerase activity. Telomerase activity was detected in oral leukoplakia (75%), oral squamous cell carcinoma (S.C.C.) (66.7%). Both hTEP1 and hTR expression was detected in all tissue samples tested including normal gingiva. On the other hand, hTERT expression was detected in 12 of 22(54.5%) oral leukoplakia and SCC tissues and negative in normal gingiva samples. In addition, its expression of hTERT was correlated well with telomerase activity. hTERT expression and telomerase activation thus may be a early event in the process of oral carcinogenesis.
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