THE STUDY OF SEX DIFFERENCE IN HEPATOCARCINOGENESIS-ANALYSIS USING TGF alpha TRANSGENIC MICE-
| Project/Area Number |
07670562
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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 |
Gastroenterology
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| Research Institution | GUNMA UNIVERSITY |
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Principal Investigator |
TAKAGI Hitoshi GUNMA UNIVERSITY SCHOOL OF MEDICINE,THE FIRST DEPARTMENT OF INTERNAL MEDICINE,TEACHING ASSOCIATE, 医学部, 助手 (20251093)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | TGF alpha / hepatoma / gender / transgenic mice / androgen / LH-RH-agonist / p450 |
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| Research Abstract |
We tested the mechanism of male predominant hepatocarcino-genesis using transforming growth factor alpha transgenic mice which also developed liver tumor preferentially in male. Serum level of testosteron was 1.38ng/dl in control male mice and 29.7ng/dl in transgenic mice. We observed transgenic male mice for 15 months after the treatment as follows ; sham operated (no treatment) (S), castrated (C) and castrated and 5 alpha-dihydrotestosteron complement (C+D). Serum level of testosteron was increased C-C+D-S in this order. On the other hand, body weight and liver weight were lower in (C) than in (C+D) and (S). Seven liver tumors were developed in 6 (S), 2 in (C) and 9 of 6 (C+D) transgenic mice. Two liver tumors in (C) were smaller than those in (S) and (C+D). PCNA staining showed higher labelling index in (S) and (C+D) than (C) in both liver tumors and surrounding liver tissues. Anti-androgenic effect of LH-RH agonist, leuprorelin acetate, was administered to the transgenic mice and suppressed the liver tumor formation. These results suggest the androgen has promotor like effect in hepatic tumorigenesis in TGF alpha transgenic mice and TGF alpha may enhance the androgen production. this evidence was supported by the results of the study using the cell lines (AML12) established from TGF alpha transgenic liver. AML12 produced TGF alpha in culture supernatant higher in the presense of androgen but not changed in that of estrogen. p450 2A family, which is a catabolic enzyme of the liver and highly expressed in female, was significantly expressed in MT42 male liver especially in liver tumors of transgenic mice. The result demonstrated the relationship of TGF alpha-androgen-p450 2A in liver tumor formation.
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Report
(3 results)
Research Products
(26 results)
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[Publications] Ichikawa T,Takehara K,Takagi H,Arai H,Shimoda R,Matsumoto T,Saito S,Yuasa T,Arai T,Nagamine T,Yamada S,Mori M.: "Effect of the EGF-receptor-inhibit or on primary cultured hepatocytes isolated from transgenic mice of transforming growth factor alpha." Int Hepatol Commun. 3 : suppl. s74 (1995)
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