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首页> 外文期刊>British Journal of Cancer >Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor expression and mitogenic responses in human breast cancer cell lines
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Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor expression and mitogenic responses in human breast cancer cell lines

机译:甲状旁腺激素(PTH)/ PTH相关蛋白(PTHrP)受体在人乳腺癌细胞系中的表达和促有丝分裂反应

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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.
机译:先前的报道显示乳腺癌细胞在体内和体外产生甲状旁腺激素相关蛋白(PTHrP)。我们已经研究了人乳腺癌细胞系MCF-7,ZR-75-1,T-47-D,SK-BR-3,Hs578T和MDA-MB231对PTH / PTHrP受体的表达。使用逆转录聚合酶链反应(RT-PCR)和Southern印迹分析,我们在MCF-7,SK-BR-3和MDA-MB231细胞中检测了受体的转录本。在ZR-75-1和Hs578T细胞中没有受体mRNA的证据。此外,对来自MCF-7细胞的mRNA进行Northern印迹分析表明,两个转录本分别为1.5和2.4 kb,编码PTH / PTHrP受体。乳腺癌细胞系中PTH / PTHrP受体mRNA的表达也与PTHrP转录本的检测有关。 RT-PCR在MCF-7,ZR-75-1,T-47-D和Hs578T细胞中显示了PTHrP mRNA,而在SK-BR-3和MDA-MB231细胞中则没有。 [3H]胸苷和溴脱氧尿苷掺入研究补充了受体转录物的检测,其中在MCF-7细胞中观察到对PTH和PTHrP的促有丝分裂反应,而在Hs578T细胞中未观察到。响应PTH(1-34)和PTHrP(1-34),静态MCF-7细胞以类似的剂量依赖性方式(1.6-100 ng ml-1)增殖。 Hs578T细胞未观察到这些肽的促有丝分裂作用。另外,响应PTHrP(1-34),在MCF-7和Hs578T细胞中测量了细胞内cAMP的水平。在MCF-7细胞中,使用100 ng ml-1 PTHrP(1-34)的cAMP显着增加。乳腺癌细胞表达PTH / PTHrP受体表明PTHrP可能是乳腺癌的旁分泌/自分泌调节剂。

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