SOX9 and SOX10 but Not BRN2 Are Required for Nestin Expression in Human Melanoma Cells
SOX9 and SOX10 but Not BRN2 Are Required for Nestin Expression in Human Melanoma Cells
复制标题
DOI：
10.1038/jid.2008.316
复制
发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Berking, Carola
中科院分区：
文献类型：
--
作者：
Flammiger, Anna;Besch, Robert;Berking, Carola
巢蛋白是一种中间丝蛋白，也是神经外胚层干细胞的标志物，表明其具有多潜能和再生能力。在黑色素瘤组织中，巢蛋白的重新表达与肿瘤的进展有关。Nestin神经增强子的激活依赖于III类POU转录因子的结合，其中Brain-2(Brn2)起关键作用。我们发现几乎所有13个不同进展阶段的黑色素瘤细胞系中都有巢蛋白和Brn2的mRNA，但表达水平并不相关。在13株黑色素瘤细胞系中，11株表达Nestin蛋白，7株表达Brn2蛋白，且与肿瘤分期无关。小干扰RNA下调Brn2的表达不会改变黑色素瘤细胞中Nestin的表达。然而，POU蛋白，如Brn2，通常通过与Sry-box(Sox)家族的转录因子结合到附近的DNA位点来发挥作用。Sox9和Sox10已被证明在黑素细胞前体细胞中表达，而Sox10在分化过程中下调。我们现在展示了SOX9和SOX10蛋白在黑色素瘤组织和细胞系中的表达。SOX9和SOX10的下调显著降低了黑色素瘤细胞中巢蛋白的水平。因此，在人类黑色素瘤中，巢蛋白的表达似乎需要SOX9和SOX10，而不是Brn2。
Nestin is an intermediate filament protein and a marker of neuroectodermal stem cells indicating multipotentiality and regenerative capability. In melanoma tissues, nestin re-expression was correlated with tumor progression. Activation of the nestin neural enhancer was shown to be dependent on the binding of class III POU transcription factors, with brain-2 (BRN2) suggested to play a key role. We found both nestin and BRN2 mRNA in almost all of 13 analyzed melanoma cell lines of different progression stages, but expression levels did not correlate. Nestin protein was detected in 11 of 13 and BRN2 protein in 7 of 13 melanoma cell lines independent of progression stage. Downregulation of BRN2 by small-interfering RNA did not alter nestin expression in melanoma cells. However, POU proteins, such as BRN2, commonly cooperate with transcription factors of the Sry-box (SOX) family by binding to a nearby DNA site necessary for their action. SOX9 and SOX10 have been shown to be expressed in melanocyte precursors, with SOX10 downregulated upon differentiation. We now demonstrate SOX9 and SOX10 protein expression in melanoma tissues and cell lines. Downregulation of SOX9 and of SOX10 markedly decreased nestin levels in melanoma cells in a cooperative manner. Thus, SOX9 and SOX10 but not BRN2 seem to be required for nestin expression in human melanoma.