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Parathyroid hormone-related protein mRNA expression and oral cancer progression

甲状旁腺激素相关蛋白 mRNA 表达与口腔癌进展

基本信息

批准号：
05557081
负责人：
HORIUCHI Noboru
金额：
$ 6.72万
依托单位：
Ohu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05557081/
关键词：
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

项目摘要

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.

甲状旁腺素相关蛋白（PTHrP）最初是从恶性高钙血症患者的鳞状细胞癌中分离出来的。PTHrP与甲状旁腺激素（PTH）具有相似的生化特性，如骨吸收、磷酸盐尿和增加1 α，25-二羟维生素D_3 [1，25（OH）_2D_3]的产生。本研究的主要结果如下：1.口腔癌组织中PTHrP mRNA的表达水平在进展期口腔癌中明显升高，但并不一定伴有高钙血症; 2.研究了口腔癌细胞系HSC-3中PTHrP的表达调控。为研究PTHrP表达与血清1，25（OH）_2D_3的关系，建立了一种简便、灵敏的1，25（OH）_2D_3测定方法。重点研究了1，25（OH）_2D_3降解的关键酶24-羟化酶。PTH和PTHrP抑制24-羟化酶的活性，但不影响基因表达，PTHrP基因表达可能是口腔癌发生发展的一个重要参数。我们正在进行的调查PTHrP和肿瘤标志物基因表达在不同阶段的癌症活检之间的关系。