| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Role of tumor suppressor genes on tumorigenesis of human pituitary adenomas was studied. Abnormalities of tumor suppressor genes related with cell cycle regulation including p16, p15, p27 genes were analized on 33 surgically resected pituitary adenomas (2 familial and 31 sporadic cases). Loss of heterozygosity (LOH) on 9p21-22, in which p16 and p15 geses are located, was detected in 2 case, and polymorphism of p27 gene was noted in 3 cases. However, no tumor specific mutations were found in all 33 cases, indicating that these tumor suppressor genes may not play a role on tumorigenesis of pituitary adenomas. On the other hand, trisomy of chromosome 12, on which p27 gene is located, was found in all 5 cases studied by FISH method, suggesting a possible relation to the occurrence of pituitary adenomas.
Abnormalities of MEN 1 gene that is also considered to be a tumor suppressor gene were studied on 31 sporadic pituitary adenomas. LOH on 11qI3 was detected in 1 case and trisomy of chromosome 11 was noted by FISH method in 2 cases. MEN 1 gene mutation was detected in case with LOH, but the remaining 30 cases spared MEN 1 gene mutations, indicating that MEN 1 gene mutations may not be involved in tumorigenesis of sporadic pituitary adenomas.
A significant relationship (p<0.0001) between the expression of CRHmRNA by in situ hybridization and the proliferation rate measured by MIB - 1 index was found in 44 ACTH-producing rug pituitary adenomas. These findings suggest that hypothalamic hormone CRH is produced by adenoma cells and that CRH may play a roll on the growth of pitutiary adenomas in an autocrine manner.
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