Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma

Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma
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DOI:
10.1111/j.1600-0625.2009.00991.x
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发表时间:
2010-08-01
影响因子:
3.6
通讯作者:
Berking, Carola
Berking, Carola
中科院分区:
医学2区
文献类型:
--
作者:
Bakos, Renato M.;Maier, Tanja;Berking, Carola

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巢蛋白是一种在增殖的神经前体细胞中表达的中间丝,被认为是干细胞的标志物。巢蛋白也存在于黑色素瘤中,我们最近证明其在黑色素瘤细胞系中的表达受转录因子SOX 9和SOX 10的调节,而不是BRN2。在这项研究中,巢蛋白,BRN2,SOX 9和SOX 10在黑色素瘤(n = 78)和黑色素细胞痣(n = 26)的组织中的表达水平进行了分析,通过免疫组化。所有蛋白质在原发性和转移性黑色素瘤中均高度表达,除BRN2外,在黑色素细胞痣中的表达水平要低得多。在原发性黑色素瘤中发现巢蛋白与SOX 9和SOX 10的显著共表达,证实了我们的体外数据。与临床病理资料的相关性分析显示,nestin与原发肿瘤中溃疡的存在显著相关,SOX 9与更晚期的疾病相关。我们的数据显示,SOX 9和SOX 10在黑色素瘤中高度表达,并且似乎在巢蛋白表达中具有调节作用。分别与溃疡和晚期肿瘤的相关性表明,巢蛋白和SOX 9可能是黑色素瘤的阴性预后标志物。
Nestin is an intermediate filament expressed in proliferating neural progenitor cells and has been considered as a stem cell marker. Nestin is also found in melanoma and we recently demonstrated that its expression in melanoma cell lines is regulated by the transcription factors SOX9 and SOX10, but not BRN2. In this study, the expression levels of nestin, BRN2, SOX9 and SOX10 were analysed in tissues of melanoma (n = 78) and melanocytic nevi (n = 26) by immunohistochemistry. All proteins were highly expressed in primary and metastatic melanomas and, apart from BRN2, showed much lower levels in melanocytic nevi. Significant coexpression of nestin with SOX9 and SOX10 was found in primary melanoma confirming our in vitro data. Correlation analysis with clinicopathological data revealed that nestin was significantly associated with presence of ulceration in primary tumors and SOX9 with more advanced stage of disease. Our data reveal that SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in nestin expression. The association with ulceration and advanced-stage tumors, respectively, suggests that nestin and SOX9 may be negative prognostic markers in melanoma.