2002 Fiscal Year Final Research Report Summary
Growth factor induced by high phosphate in cultured human parathyroid gland : gene analysis using cDNA microarray
| Project/Area Number |
13671164
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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 | Tokyo Women's Medical University |
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Principal Investigator |
SATO Kanji Tokyo Women's Medical University, Institute of Clinical Endocrinology, Associate Professor, 医学部, 助教授 (60138857)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Parathyroid gland / cDNA microarray / Phosphate / PTH / growth factors / cytokines / MEN1 / prion |
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| Research Abstract |
A patient with hypophosphatemic osteomalacia, who was treated with high phosphate, developed tertiary hyperparathyroidism. Gene analysis of the four hyperparathyroid glands revealed several gene mutations, suggesting that high phosphate concentration stimulated parathyroid growth, accompanied with mutations of oncogenes and tumor suppressor genes (I.d. MEN1) (Reference 1).
To clarify phosphate-induced cell proliferation of parathyroid gland, we established organ culture of parathyroid tissue obtained from patient with primary or secondary hyperparathyroidism. In this organ culture, intact PTH was actively secreted for more than 1 month. Intact PTH secretion was inhibited at high calcium concentration at physiologically attainable Ca^<++> levels. When parathyroid tissue were cultured with high phosphate medium, intact PTH secretion was increased and cell proliferation was also stimulated. Gene analyses of DNA microarray revealed that several growth factors (IGF-1, AIF1, FIGF) and cytokines were increased. We are analyzing 4800 genes induced by high phosphate since a greater amount of total RNA (>30μg) is available at the present time. We expect that these new findings will contribute to elucidate the mechanism of parathyroid cell proliferation, and to develop new treatments for secondary hyperparathyroidism.
In early series of this experiments in which only a small amount of total RNA was obtained from parathyroid cell culture, we analyzed 2400 genes in thyroid follicles in which a large amount of total RNA was easily obtained, and found that several genes (including prion) are induced by TSH (reference 2 & 3).
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[Publications] Sato K, Obara T, Yamazaki K, Kanbe M, Nakajima K, Yamada A, Yanagisawa T, Kato Y, Nishikawa T, Takano K: "Somatic mutations of the MEN1 gene and microsatellite instability in tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia"J Clin Endocrinol Metab. 86. 5564-5571 (2001)
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