Calcitonin-suppressed expression of parathyroid hormone-related protein in breast cancer cells
Calcitonin-suppressed expression of parathyroid hormone-related protein in breast cancer cells
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DOI：
10.1006/bbrc.1999.1659
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发表时间：
1999-11-11
影响因子：
3.1
通讯作者：
Bucht, E
中科院分区：
文献类型：
--
作者：
Rong, HQ;Ji, H;Bucht, E
甲状旁腺激素相关蛋白（PTHrP）是恶性肿瘤体液高钙血症（HHM）背后的关键因素。它在大多数乳腺肿瘤中产生，可能是乳腺骨骼转移的重要局部介质；癌症。在循环 PTHrP 不增加的情况下，PTHrP 可能介导局部骨质破坏。降钙素（CT）用于治疗HRM，但有数据表明CT可以在体外增加PTHrP的表达和分泌。因此，我们研究了 GT 对 MCF-7 乳腺癌细胞中 PTHrP 基因表达和分泌的影响。与各自的对照相比，与 10 nM 鲑鱼降钙素 (sCT) 孵育 4、8 和 16 小时后，PTHrP mRNA 显着下降。与 0.1 至 10 nM 的 sCT 孵育 16 小时后，PTHrP mRNA 也显着降低，且呈剂量依赖性。条件培养基中的 PTHrP 水平也以类似的剂量依赖性方式降低。腺苷酸环化酶激动剂毛喉素可剂量依赖性地降低 PTHrP mRNA。在暴露于不同浓度的 sCT 15 分钟的细胞中，cAMP 水平呈剂量依赖性增加。总之，sCT可以抑制MCF-7乳腺癌细胞中PTRrP基因的表达。抑制作用可能主要通过 cAMP-蛋白激酶 A 途径发挥。 (C) 1999 年学术出版社。
Parathyroid hormone-related protein (PTHrP) is a key factor behind humoral hypercalcemia of malignancy (HHM). It is produced in most breast tumors and may be an important local mediator of skeletal metastases due to breast; cancer. PTHrP may mediate local bone destruction in the absence of increased circulating PTHrP. Calcitonin (CT) is used for treatment of HRM, but there are data showing that CT can increase PTHrP expression and secretion in vitro. We have therefore studied the effect of GT on PTHrP gene expression and secretion in MCF-7 breast cancer cells. PTHrP mRNA decreased significantly after 4, 8, and 16 h incubation with 10 nM salmon calcitonin (sCT) when compared with the respective controls. PTHrP mRNA also decreased significantly and dose-dependently after incubation with sCT at 0.1 to 10 nM for 16 h. The PTHrP levels in the conditioned medium also decreased in a similar dose-dependent manner. The adenylate cyclase agonist forskolin lowered the PTHrP mRNA dose-dependently. In cells exposed to varying concentrations of sCT for 15 min, the cAMP levels increased dose-dependently. In conclusion, sCT can suppress PTRrP gene expression in MCF-7 breast cancer cells. The suppressive effect is probably exerted mainly via the cAMP-protein kinase A pathways. (C) 1999 Academic Press.