| Project/Area Number |
05557081
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Ohu University |
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Principal Investigator |
HORIUCHI Noboru Dept.of Biochemistry, Ohu University School of Dentistry, Professor, 歯学部, 教授 (00107294)
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| Co-Investigator(Kenkyū-buntansha) |
OHKAWA Hiroyuki Chugai Pharmaceutical Co.Fuji-Gotenba Research Laboratories, Associate Director, 富士御殿場研究所・創薬推進部, 副部長
AKENO Nagako Dept.of Biochemistry, Ohu University School of Dentistry, Assistant, 歯学部, 助手 (30231856)
ABE Masatoshi Dept.of Biochemistry, Ohu University School of Dentistry, Lecturer, 歯学部, 講師 (10254872)
OHNO Tomoya Dept.of Oral Surgery II,Ohu University School of Dentistry, Professor, 歯学部, 教授 (50094941)
西勝 祥子 奥羽大学, 歯学部, 助手 (30170484)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | PTHrP / Oral cancer / Tumor marker / Hypercalcemia / Vitamin D-24-hydroxylase / Gene expression / 1alpha, 25-dihydroxyvitamin D_3 / Parathyroid hormone receptor / 増殖因子 / PTH_rP |
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| Research Abstract |
Parathyroid hormone-related protein (PTHrP) was originally isolated from sequamous carcinoma from patients with hypercalcemia of malignancy. PTHrP and Parathyroid hormone (PTH) share similar biochemical properties such as bone resorption, phosphaturia and increased production of 1alpha, 25-dihydroxyvitamin D_3 [1,25 (OH)_2D_3]. Moreover, PTHrP acts through the same membrane receptor as PTH.In the present investigation, following results were obtained.
1.PTHrP mRNA abundance in biopsies was increased in progressive oral cancer, although hypercalcemia did not emerge from all of the patients.
2.The regulation of PTHrP expression was studied in oral cancer cell line (HSC-3). The active form of vitamin D,1,25 (OH)_2D_3, inhibited PTHrP gene expression and the production in a dose-dependent manner.
3.To study the relationship between PTHrP expression and serum 1,25 (OH)_2D_3, a simple and sensitive 1,25 (OH)_2D_3 assay was developed.
4.The influence of PTHrP and PTH on 1,25 (OH)_2D_3 metabolism was assessed. A critical enzyme for 1,25 (OH)_2D_3 degradation, 24-hydroxylase, was focused. PTH and PTHrP inhibited the activity of 24-hydroxylase but did not affect the gene expression.
PTHrP gene expression may be very important for a parameter of the progress of oral cancer. We are proceeding with the investigation on the relationship between PTHrP and tumor marker gene expression in various stages of cancer biopsies.
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