Zuidervaart W, van Nieuwpoort F, Stark M, Dijkman R, Packer L, Borgstein A-M, Pavey S, van der Velden P, Out C, Jager M J, Hayward N K, Gruis N A
Department of Ophthalmology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
Br J Cancer. 2005 Jun 6;92(11):2032-8. doi: 10.1038/sj.bjc.6602598.
In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.
与皮肤黑色素瘤不同，没有证据表明BRAF突变参与葡萄膜黑色素瘤中丝裂原活化蛋白激酶（MAPK）途径的激活，尽管越来越多的证据表明该途径在后者肿瘤中经常被激活。在本研究中，我们对一组11个葡萄膜黑色素瘤细胞系和19个原发性葡萄膜黑色素瘤肿瘤进行了RAS和BRAF基因的突变分析。此外，对MAPK途径的下游成员进行了蛋白质印迹和免疫组织化学分析，以评估这些成分各自的作用。在三个RAS基因家族成员中均未发现突变，只有一个细胞系携带BRAF突变（V599E）。尽管如此，丝裂原活化蛋白激酶/细胞外信号调节激酶激酶（MEK）、ERK和ELK在所有样本中均持续激活。这些数据表明，MAPK途径的激活通常参与葡萄膜黑色素瘤的发生发展，但发生机制与皮肤黑色素瘤不同。
