1996 Fiscal Year Final Research Report Summary
Study of rearrangement of the ret and trk photo-oncogenes in rat thyroid carcinomas-induced in vivo by N-bis (2-hydroxypropyl) nitrosamine.
| Project/Area Number |
07670257
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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 |
Experimental pathology
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| Research Institution | Second Department of Pathology, Nara Medical University |
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Principal Investigator |
KITAHORI Yoshiteru Nara Medical University, Second Department of Pathology, Assistant, 医学部, 助手 (30221211)
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| Project Period (FY) |
1995 – 1996
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| Keywords | thyroid carcinoma / ret proto-oncogene / trk propto-oncogene / ras oncogene / p53 oncogene / Gas |
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| Research Abstract |
We investigated the rearrangements of the ret and trk proto-oncogenes in the rat thyroid carcinomas in vivo induced N-bis (2-hydroxypropyl) nitromasmine. RNAs from 11 rat thyroid carcinomas were analyzed by Northern blot, the Multiplex RT-PCR and 5-REAC methods. Rearrangements of the ret and trk proto-oncogenes were not detected in all samples.
Moreover, we investigated the alteration of ras, p53, TSH-R and Gas genes in all carcinomas by SSCP and sequence methods. Mutations were identified using SSCP,RFLP and DNA sequencing analysis. All of the neoplasms could be shown to have mutations in Ki-ras codon 12 (G to A)(Gly to Ser). At the same time, point mutations in Gas codon 201 (G to A) were detected in three carcinomas, resulting in a heterozgous alteration (Arg to His). One TSH-R gene mutation was found with a base substitution in codon 636 (C to T) but no amino acid change. No p53 gene mutations were detected.
These results suggest that the point mutations of ras and Gas genes rather than the rearrangement of et and trk proto-oncogenes may play an important role in the pathogenesis of thyroid carcinoma.
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[Publications] Kitahori, Y., Naito, H., Konishi, N., Ohnishi, T., Shirai, T.and Hiasa, Y.: "Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine-initiated thyroid, kidney and lung tumors in Wistar rats" Cancer Letters. 96. 155-161 (1995)
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[Publications] Kitahori, Y., Naitoh, H., Konishi, N., Fukushima, M., Ohnishi, T.and Hiasa, Y.: "G*A mutation of ras genes and infrequent p53 gene mutation in rat transplantable thyroid carcinoma line from tumors induced in vivo by N-bis (2-hydroxypropyl) nitrosamine" Cancer Letters. 100. 55-62 (1996)
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[Publications] Nakahashi, K., Kitahori, Y., Konishi, N., Ohnishi, T., Sugimura, M.and Hiasa, Y.: "Establishment of a rat thyroid carcinoma cell line in vitro demonstrating jigh DNA synthesis in response to insuline-like growth factor I" Cancer Letters. 101. 247-255 (1996)
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