Wnt5a-Ca^(2+)-CN-NFAT通路信号分子在黑素瘤中的表达  

The expression of signaling molecules of Wnt5a-Ca^(2+)-CN-NFAT pathway in melanoma

作　　者：徐玉荣[1] 刘启方[1] 廖文俊[1] 

机构地区：[1]第四军医大学西京皮肤医院,西安710032

出　　处：《实用皮肤病学杂志》2015年第6期406-410,共5页Journal of Practical Dermatology

摘　　要：目的探讨Wnt5a-Ca2+-CN-NFAT通路主要信号分子在正常人黑素细胞及不同黑素瘤细胞系中的激活状态。方法选取正常人原代黑素细胞(MC)及来源于原位(WM793B)、侵袭性(LIBR)及转移性(SK-MEL-5)黑素瘤细胞系和色素痣、黑素瘤组织,采用逆转录-聚合酶链反应(RT-PCR)、蛋白质印迹法(Western blot)、激光共聚焦及免疫组化法检测细胞及组织中该通路主要信号分子的表达情况。结果与正常人黑素细胞相比,在不同黑素瘤细胞系中该通路主要信号分子Wnt5a、散乱蛋白2(DVL2)、钙调神经磷酸酶(calcineurin,CN)、活化T细胞核因子2(NFAT2)、环氧合酶-2(COX-2)、血管内皮细胞生长因子A(VEGF-A)、黏着斑蛋白(vinculin)及波形蛋白(vimentin)明显高表达,且Ca2+浓度较高;CN-B、NFAT2在色素痣中均为阴性表达,而在黑素瘤组织中多数呈阳性表达(P<0.001)。在侵袭性及转移性黑素瘤中的表达强度明显高于原位黑素瘤。结论在黑素瘤的发生、发展过程中,Wnt5aCa2+-CN-NFAT信号通路可能被激活,并在黑素瘤的侵袭和转移中发挥重要作用。Objective To investigate the expression of main signaling molecules of Wnt5a-Ca2＋-CN-NFAT signaling pathway in normal melanocytes and melanoma cells. Methods Expression of main signaling molecules was detected by laser confocal, immunohistochemistry, RT-PCR and Western blot in primary cultured melanocytes from healthy persons, WM793B, Libr, Sk-mel-5 melanoma cells, pigmented nevus and melanoma tissue. Results The expression ofWnt5a, DVL2, calcineurin, NFAT2, COX-2, VEGF-A, Vinculin and Vimentin was significantly higher in melanoma cells than in normal melanocytes. The result of Ca2＋ concentration was similar to the expression of those molecules. The expression of calcineurin-B and NFAT2 was positive in most melanoma tissues but negative in pigmented nevus （P〈0.001）. The expression intensity of calcineurin-B and NFAT2 was significantly higher in invasive melanoma and metastatic melanoma than in melanoma in situ. Conclusion The Wnt5a-Ca2＋-CN-NFAT signaling pathway may be activated in melanoma and play a key role in invasion and metastasis of melanoma.

关 键 词：黑素瘤 钙调神经磷酸酶 活化T细胞核因子 Wnt5a-Ca2+-CN-NFAT通路 

分 类 号：R739.5[医药卫生—肿瘤]