Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor expression and mitogenic responses in human breast cancer cell lines.
Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor expression and mitogenic responses in human breast cancer cell lines.
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DOI：
10.1038/bjc.1995.282
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发表时间：
1995-07
影响因子：
8.8
通讯作者：
Gallagher JA
中科院分区：
文献类型：
--
作者：
Birch MA;Carron JA;Scott M;Fraser WD;Gallagher JA
先前的报道显示乳腺癌细胞在体内和体外产生甲状旁腺相关蛋白（PTHrP）。我们研究了人乳腺癌细胞系MCF-7、ZR-75-1、T-47-D、SK-BR-3、Hs 578 T和MDA-MB 231中PTH/PTHrP受体的表达。采用逆转录-聚合酶链反应（RT-PCR）和Southern印迹分析，检测了MCF-7、SK-BR-3和MDA-MB 231细胞中该受体的转录本。ZR-75-1和Hs 578 T细胞中未见受体mRNA表达。此外，来自MCF-7细胞的mRNA的北方印迹分析显示了编码PTH/PTHrP受体的1.5和2.4kb的两个转录本。乳腺癌细胞系PTH/PTHrP受体mRNA的表达也与PTHrP转录本的检测相关。RT-PCR检测到MCF-7、ZR-75-1、T-47-D和Hs 578 T细胞中PTHrP mRNA的表达，而SK-BR-3和MDA-MB 231细胞中PTHrP mRNA的表达不明显。[3 H]胸苷和溴脱氧尿苷掺入的研究，其中观察到的促有丝分裂反应，以PTH和PTHrP在MCF-7细胞，但不是在Hs 578 T细胞的受体转录本的检测进行了补充。在PTH（1-34）和PTHrP（1-34）的作用下，静止的MCF-7细胞以相似的剂量依赖性方式增殖（1.6-100 ng ml-1）。用Hs 578 T细胞没有观察到这些肽的促有丝分裂作用。此外，在MCF-7和Hs 578 T细胞中测量响应PTHrP（1-34）的细胞内cAMP水平。在MCF-7细胞中，100 ng/ml PTHrP（1-34）时cAMP显著升高。乳腺癌细胞表达PTH/PTHrP受体，提示PTHrP可能是乳腺癌的旁分泌/自分泌调节因子。
Previous reports have shown the production of parathyroid hormone-related protein (PTHrP) by breast cancer cells in vivo and in vitro. We have investigated the expression of the PTH/PTHrP receptor by the human breast cancer cell lines MCF-7, ZR-75-1, T-47-D, SK-BR-3, Hs578T and MDA-MB231. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis, we detected transcripts for the receptor in MCF-7, SK-BR-3 and MDA-MB231 cells. There was no evidence of receptor mRNA in ZR-75-1 and Hs578T cells. Furthermore, Northern blot analysis of mRNA from MCF-7 cells showed two transcripts of 1.5 and 2.4 kb which coded for the PTH/PTHrP receptor. Expression of PTH/PTHrP receptor mRNA by the breast cancer cell lines was also correlated with the detection of PTHrP transcripts. RT-PCR demonstrated PTHrP mRNA in MCF-7, ZR-75-1, T-47-D and Hs578T cells, but not in SK-BR-3 and MDA-MB231 cells. The detection of receptor transcripts was complemented by [3H]thymidine and bromodeoxyuridine incorporation studies, in which mitogenic responses to PTH and PTHrP were observed in MCF-7 cells but not in Hs578T cells. In response to both PTH(1-34) and PTHrP(1-34), quiescent MCF-7 cells proliferated in a similar dose-dependent manner (1.6-100 ng ml-1). No mitogenic effects of these peptides were observed with Hs578T cells. In addition, levels of intracellular cAMP were measured in MCF-7 and Hs578T cells in response to PTHrP(1-34). In MCF-7 cells there was a significant rise in cAMP with 100 ng ml-1 PTHrP(1-34). The expression of PTH/PTHrP receptor by breast cancer cells suggests that PTHrP may be a paracrine/autocrine regulator of breast carcinoma.