XAF1 expression is significantly reduced in human melanoma
XAF1 expression is significantly reduced in human melanoma
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DOI：
10.1111/j.0022-202x.2004.23467.x
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发表时间：
2004-12-01
影响因子：
6.5
通讯作者：
Li, G
中科院分区：
文献类型：
--
作者：
Ng, KCP;Campos, EI;Li, G
凋亡过程的失调可能是导致黑色素瘤恶性本质的关键因素之一，其特征是强烈的化疗耐药性。X-linked inhibitor of apoptosis protein （XIAP）通过抑制多种半胱天冬酶抑制细胞凋亡。最近，已发现XIAP-associated factor 1 （XAF1）是一种XIAP结合蛋白，可拮抗XIAP的抗凋亡活性。在这项研究中，我们试图确定XAF1在黑色素瘤进展中的作用。分析XAF1 mRNA在黑色素瘤细胞系中的表达，16个细胞系中有15个XAF1 mRNA表达下调。接下来，我们在40例良性痣和70例原发性黑色素瘤的组织芯片上评估了XAF1蛋白的表达。结果显示，与良性黑色素细胞痣相比，XAF1在黑色素瘤组织中的表达明显降低（p < 0.05）。我们的数据还表明，在肿瘤细胞的细胞核和细胞质中，XAF1的表达均显著降低（p < 0.0001）。然而，XAF1表达的降低与肿瘤厚度和5年生存率无显著相关性。需要进一步的研究来了解控制XAF1在肿瘤组织中选择性表达缺失的分子机制。
Deregulation of apoptotic processes is likely one of the key factors contributing to the malignant nature of melanoma marked by strong chemoresistance. X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis through the inhibition of various caspases. Recently, XIAP-associated factor 1 (XAF1) has been identified as a XIAP-binding protein that antagonizes the anti-apoptotic activity of XIAP. In this study, we sought to determine the role of XAF1 in melanoma progression. Analysis of XAF1 mRNA expression in melanoma cell lines revealed that XAF1 mRNA was downregulated in 15 of 16 cell lines examined. We next evaluated XAF1 protein expression on a tissue microarray representing 40 benign nevi and 70 primary melanomas. Our results showed that XAF1 expression in melanoma tissues was significantly reduced compared with benign melanocytic nevi (p < 0.05). Our data also demonstrated that the substantial reduction of XAF1 expression occurred in both nucleus and cytoplasm in the tumor cells (p < 0.0001 for both). Reduced XAF1 expression, however, was not significantly correlated with tumor thickness and 5-y patient survival. Further studies are required to understand the molecular mechanisms governing the selective loss of XAF1 expression in the tumor tissue.