2006 Fiscal Year Final Research Report Summary
Function of parafibromin inhibiting parathyroid tumorigenesis
| Project/Area Number |
17590963
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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 |
Endocrinology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YOSHIMOTO Katsuhiko The University of Tokushima Graduate School, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (90201863)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Takeo The University of Tokushima Graduate School, Institute of Health Biosciences, Research Associate, 大学院ヘルスバイオサイエンス研究部, 助手 (10350399)
MIZUSAWA Noriko The University of Tokushima Graduate School, Institute of Health Biosciences, Research Associate, 大学院ヘルスバイオサイエンス研究部, 助手 (80254746)
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| Project Period (FY) |
2005 – 2006
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| Keywords | parathyroid / hereditary tumor / endocrine / oncogene / tumor suppressor gene |
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| Research Abstract |
Germline mutations of HRPT2 were found in 2 of 11 FIHP families and 1 of 2 HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas, and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in 2 of 5 parathyroid tumors in a family with 518-521 del mutation. Biallelic inactivation of HRPT2 by a combination of germline mutation and somatic mutation was confirmed in parathyroid tumors. The finding that 2 families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT.
Parafibromin is a 531-amino acid protein product encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of parafibromin overexpression on cell proliferation, we performed cell proliferation assay in four different cell lines. Transient parafibromin overexpression inhibited cell growth in HEK293 and NIH3T3 cells, whereas enhanced cell growth in SV40 large T antigen expressing-cell lines such as 293FT and COS7 cells. In 293FT cells, the parafibromin was found to interact with SV40 large T antigen and overexpression of parafibromin promoted entry into S phase, implying that interaction between parafibromin and SV40 large T antigen enhanced cell cycle progression. Based on these we conclude that tumor suppressor protein, parafibromin, acts a positive regulator of cell growth such as oncoproteins at the presence of SV40 large T antigen.
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Research Products
(12 results)
