NFATc4在不同恶性黑色素瘤亚型中的表达与功能研究  

Function and mechanism of NFATc4 in malignant melanoma with different subtypes

作　　者：饶玮 冯靖懿 王祎琳 杜治民 马冠毅 苏清 赵华[2] RAO Wei;FENG Jingyi;WANG Yilin;DU Zhimin;MA Guanyi;SU Qing;ZHAO Hua(Chinese PLA Medical School,Beijing 100853,China;Department of Dermatology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心皮肤科,北京100853 [3]首都医科大学中医药学院,北京100069

出　　处：《解放军医学院学报》2024年第8期891-897,共7页Academic Journal of Chinese PLA Medical School

摘　　要：背景研究表明活化T细胞核因子c4(nuclear factor of activated T-cells,cytoplasmic 4,NFATc4)的激活表达可促进恶性黑色素瘤的发生发展,但NFATc4在黑色素瘤中的靶向分子及其在不同类型黑色素瘤中的表达尚不明确。目的探讨NFATc4及其靶标MMP2、COX2在黑色素瘤细胞及不同黑色素瘤亚型中的表达水平及其与临床病理特征的关系。方法建立NFATc4过表达的黑色素瘤细胞系,检测NFATc4的功能及其与MMP2和COX2的表达相关性;利用免疫组织化学法检测皮肤肢端黑色素瘤、皮肤非肢端黑色素瘤、鼻腔黏膜黑色素瘤石蜡组织和色素痣石蜡组织样本中NFATc4、MMP2、COX2的表达情况,并分析NFATc4、MMP2、COX2与不同类型恶性黑色素瘤临床病理特征的关系。免疫组化实验分为对照组(色素痣组)和实验组(皮肤肢端黑色素瘤组、皮肤非肢端黑色素瘤组、鼻腔黏膜黑色素瘤组)。结果NFATc4促进黑色素瘤细胞的迁移和侵袭,其表达与MMP2和COX2呈正相关。这3种分子在3种恶性黑色素瘤亚型组织中的表达均高于皮内痣(P<0.01);在肢端和黏膜黑色素瘤中的表达均高于非肢端黑色素瘤(P<0.05);NFATc4与MMP2、COX2表达水平呈正相关(P<0.01)。结论NFATc4可能通过调控MMP2、COX2参与肢端及黏膜黑色素瘤的发生及发展。Background Studies have demonstrated that the activated expression of nuclear factor of activated T-cells,cytoplasmic 4(NFATc4)can promote the progression of malignant melanoma with different subtypes.However,the target molecules of NFATc4 in melanoma and its expression across different types of melanoma remain unclear.Objective To investigate the expression levels of NFATc4 and its targets MMP2 and COX2 in melanoma cells and various melanoma subtypes,as well as their correlation with clinicopathologic features.Methods Melanoma cell lines with NFATc4 overexpression were established to assess NFATc4 function and its association with MMP2 and COX2 expression.The expressions of NFATc4,MMP2,and COX2 were examined using immunohistochemical methods in 11 cases of cutaneous acral melanomas,10 cases of cutaneous non-acral melanomas,15 cases of nasal mucosal melanoma,and 10 cases of pigmentation nevus.The correlation between NFATc4,MMP2,COX2,and clinicopathological features of different types of malignant melanoma was analyzed.Results NFATc4 was found to promote the migration and invasion of melanoma cells,with MMP2 and COX2 expression showing a positive correlation.The expression of these three molecules in the three subtypes of malignant melanoma was significantly higher than that in pigmentation nevus(P<0.01).Furthermore,the expression levels of melanomas in acral and mucosa were higher than those in non-acral melanomas(P<0.05),and NFATc4 was positively correlated with the expression levels of MMP2 and COX2(P<0.01).Conclusion These findings suggest that NFATc4,MMP2,and COX2 may play roles in the initiation and progression of acral and mucosal melanoma.However,further investigation is required to elucidate the specific mechanism of action.

关 键 词：黑色素瘤 痣 NFATc4 基质金属蛋白酶2 环氧化酶2 

分 类 号：R739.5[医药卫生—肿瘤]