| Project/Area Number |
63570545
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kitasato University |
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Principal Investigator |
ABE Yoshifumi Kitasato University, School of Medicine Assistant Professor, 医学部, 講師 (30124928)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Thyroid carcinoma / ras oncogene / GTP binding protein / 癌遺伝子 / トランスメンブレンコントロ-ル / 細胞内カルシウム / トランスメンブレンコントロール |
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| Research Abstract |
Recent data suggest that the ras oncogene products modulate the responsiveness of several enzymes in the cell membrane that respond to the extercellular singnels.
The membrane fraction were freshly prepared from six human thyroid carcinomas and adjacent normal thyroid tissues. Western blotting analysis was used to determine the amount of p21 (ras oncogene product) in membrane fraction using specific antisera (NCC-RAS-004). Levels of Gi subunit were monitored by labeling with [^<32>P] NAD and pertussis toxin. The adenyalte cylase activities were measured by RIA of the cyclic AMP generated during 30 min incubation of the membrane fraction in the presence of 10mU/ml TSH. In western blotting analysis, the monoclonal antibody NCC-RAS-004 detected clear band of p21 in membranes from both normal and carcinoma thyroid tissues. When the staining intensity of bands was examined with a densitometer, the intensity of the p21 band of carcinomas tissues was stronger by two-fold or more compared with
… More
that of adjacent normal thyroidas in 5 of 6 cases. No abnormally migrating p21 was detected in these cases. In agreement with other studies, pertussis toxin labeled a 41KDa band (Gi) in both normal and carcinoma thyroid membranes. However the membranes from carcinomas reduced the level of labeling of Gi by 50-10% in 5 of 6 cases. The level of enhanced expression of p21 were significantly correlated with the level of increased response of the adenylate cyclase to TSH and inversely related to the level of Gi assessed by ADP-ribosylation with petrussis toxin.
Our results suggest that the ras oncogene product P21 play enhancing role in adenylate cyclase system and its modulation by the G protein. Thus a ras producing cell is hypersensitive to a variety of hormones and growth factors and this hypersensitivity might contribute significantly to the oncogenicity of these proteins under physiological conditions in the whole animal. Further studies are required to clarify whether the changes in sensitivity of adenyalte cyclase activation to TSH are mediated ras oncogene or its products. Less
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