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.

甲状旁腺激素相关蛋白（PTHrP）最初是从恶性肿瘤高钙血症患者的鳞状癌中分离出来的。 PTHrP 和甲状旁腺激素 (PTH) 具有相似的生化特性，例如骨吸收、磷酸盐尿和 1α, 25-二羟基维生素 D_3 [1,25 (OH)_2D_3] 产量增加。此外，PTHrP 通过与 PTH 相同的膜受体发挥作用。在本研究中，获得了以下结果。1.进展性口腔癌中活组织检查中 PTHrP mRNA 丰度增加，尽管并非所有患者都出现高钙血症。2.在口腔癌细胞系 (HSC-3) 中研究了 PTHrP 表达的调节。维生素D的活性形式1,25(OH)_2D_3以剂量依赖性的方式抑制PTHrP基因的表达和产生。 3.为了研究PTHrP表达与血清1,25(OH)_2D_3的关系,简单的并开发了灵敏的1,25(OH)_2D_3检测方法。4.评估PTHrP和PTH对1,25(OH)_2D_3代谢的影响。 1,25 (OH)_2D_3 降解的关键酶 24-羟化酶受到关注。 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进展的一个非常重要的参数。我们正在对癌症活检各个阶段的PTHrP与肿瘤标志物基因表达的关系进行研究。