1998 Fiscal Year Final Research Report Summary
Analysis of gene mutation in ACTH producing tumor and its clinical applications.
| Project/Area Number |
09671071
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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 |
内分泌・代謝学
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| Research Institution | Teikyo University |
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Principal Investigator |
TANAKA Koshi Teikyo University, Dept.of Medicine, Professor, 医学部, 教授 (70142453)
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| Co-Investigator(Kenkyū-buntansha) |
OGINO Yoshio Teikyo Univ., Dept.of Medicine, Assistant Professor, 医学部, 助手 (80185529)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ACTH / Cushing's syndrome / Glucocorticoid / Glucocortiocid receptor / SSCP / Gene mutation |
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| Research Abstract |
Adrenocorticotropin (ACTH) producing tumor causes Gushing's syndrome that affects multiple organs including metabolic, cardiovascular, gastrointestinal, nervous, and skeletal system. Unsuccessful treatment of Gushing's syndrome results in poor prognosis in most patients. Two forms of ACTH producing tumor are known, pituitary and ectopic. Etiology of ACTH producing tumor is not well understood, which often causes difficulty in corresct diagnosis and successful therapy. One of the common features of AGTH producing tumors are the relative resistance to glucocorticoid (GG). We hypothesized that somatic mutation of GC receptor (GR) may be the cause of relative resistance to GC, which in turn results in excessive ACTH secretion. We isolated DNA from tumors and peripheral leucocytes in 5 ACTH producing tumor patients. Each exon of GR was PGR amplified and analyzed with single strand conformation polymorphism (SSCP). To detect pattern difference in SSCP, we used silver staining. We were unable to detect any difference in SSGP pattern in tumor DNA compared with leucocytes DNA from patients and normal control subjects. Direct sequence analysis was also performed for exon 2 and 3 of GR.No mutation was found. Recently, Huizenga et al. analyzed GR gene in 22 ACTH producing pituitary tumors and found no mutation in them. These results suggest that GR mutations are not a frequent cause of GR resistnace in these tumors.
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