Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment.
Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment.
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DOI：
10.1016/j.bbrc.2013.10.023
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发表时间：
2013-11-08
影响因子：
3.1
通讯作者：
Kopchick, John J.
中科院分区：
文献类型：
--
作者：
Sustarsic, Elahu G.;Junnila, Riia K.;Kopchick, John J.
越来越多的证据表明生长激素受体（GHR）参与了肿瘤的发生。虽然多项研究显示了生长激素（GH）和GHR mRNA在人类癌症组织中表达的证据，但缺乏定量，并且仅研究了少数癌症类型。美国国家癌症研究所的NCI 60小组包括来自9种人类癌症的60种癌细胞系：乳腺癌、中枢神经系统癌、结肠癌、白血病、黑色素瘤、非小细胞肺癌、卵巢癌、前列腺癌和肾癌。我们利用这个面板定量表达GHR，GH，催乳素受体（PRLR）和催乳素（PRL）mRNA的实时RT qPCR。GHR和PRLR两者在大多数癌症类型内和之间显示出广泛的表达。引人注目的是，GHR在黑色素瘤中的表达几乎是整个小组的50倍。人转移性黑色素瘤活检的分析证实了GHR基因在黑色素瘤组织中的表达。在这些人类活组织检查中，与III期相比，晚期IV期肿瘤样品中GHR mRNA的水平升高。由于黑色素瘤中高GHR的新发现，我们检查了GH治疗对三种NCI 60黑色素瘤细胞系（MDA-MB-435、UACC-62和SK-MEL-5）的影响。GH增加了三个细胞系中的两个细胞的增殖。进一步的分析显示GH以细胞系依赖性方式诱导STAT 5和mTOR的活化。总之，我们已经确定了理想的细胞系和癌症类型，以研究GH和PRL在癌症中的作用，但在很大程度上被忽视了。此外，我们发现人转移性黑色素瘤表达GHR，细胞系具有活性GHR，可以调节多种信号通路并改变细胞增殖。基于这些数据，GH可能是黑色素瘤的新的治疗靶点。
Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.
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