Parathyroid hormone-related protein mRNA expression and oral cancer progression

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，如骨吸收、磷酸尿和增加1 - α，25 -二羟基维生素D_3 [1,25 (OH)_2D_3]的产生。此外，PTHrP通过与PTH相同的膜受体起作用。在目前的调查中，获得了以下结果：尽管并非所有患者都出现高钙血症，但在进展性口腔癌的活检中PTHrP mRNA丰度增加。研究了PTHrP在口腔癌细胞株（HSC-3）中的表达调控。活性形式的维生素D 1,25 (OH)_2D_3抑制PTHrP基因的表达和产生，并呈剂量依赖性。为了研究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检测方法。观察PTHrP和PTH对1,25 (OH)_2D_3代谢的影响。重点研究了降解1,25 (OH)_2D_3的关键酶24-羟化酶。PTH和PTHrP抑制24-羟化酶活性，但不影响基因表达。PTHrP基因表达可能是口腔癌进展的一个重要参数。我们正在继续研究PTHrP与肿瘤标志物基因表达在肿瘤活检不同阶段的关系。

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.