Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter
Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter
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DOI：
10.4049/jimmunol.167.1.98
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发表时间：
2001-07-01
影响因子：
4.4
通讯作者：
Alcaïde-Loridan, C
中科院分区：
文献类型：
--
作者：
Deffrennes, V;Vedrenne, J;Alcaïde-Loridan, C
在黑色素瘤细胞系中，已经描述了两种不同的NMC II类表达模式，或者是IFN γ诱导的HLA-DR和HLA-DP表达，其中HLA-DQ的表达微弱或无效，类似于针对黑色素细胞所描述的表达，或者是组成型表达，即，IFN-γ独立，所有三种HLA-D同种型。由于后一种表型与黑色素瘤肿瘤的更快速进展相关，我们分析了不同黑色素瘤细胞系中导致这种异常MHC II类表达模式的分子机制。与这些细胞系中HLA-D基因的协调转录的证据一致，我们已经显示了CIITA（II类反式激活因子）转录物的组成型表达，CIITA被称为MHC II类表达的主开关。出乎意料的是，这些转录物起始于CIITA基因的启动子III，该启动子主要在B淋巴细胞中组成型使用。这种表达进一步显示通过作用于位于CIITA启动子III上游的增强子的因子发生，CIITA启动子III先前在上皮样细胞中被描述为IFN-γ应答序列。IFN-γ转导通路的一般异常的假设被驳回。在不相关的黑色素瘤细胞系中观察到CIITA从启动子III的组成型转录，我们提出假设，这种现象可能不是一个随机事件，但可能与黑色素瘤细胞的肿瘤状态有关。
In melanoma cell lines, two different patterns of NMC class II expression have been described, either in IFN gamma -inducible expression of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ, resembling that described for melanocytes, or a constitutive expression, i.e., IFN-gamma independent, of all three HLA-D isotypes. As this latter phenotype has been associated with a more rapid progression of melanoma tumors, we have analyzed in different melanoma cell lines the molecular mechanisms leading to this abnormal pattern of MHC class II expression. In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines, we have shown the constitutive expression of CIITA (class II transactivator) transcripts, CIITA being known as the master switch of MHC class II expression. Unexpectedly, these transcripts initiate from promoter III of the CIITA gene, a promoter that is mainly used constitutively in B lymphocytes. This expression was further shown to occur through factor(s) acting on the enhancer located upstream of CIITA promoter III, which was previously described in epithelioid cells as an IFN-gamma -response sequence. The hypothesis of a general abnormality of the IFN-gamma transduction pathway was dismissed. Constitutive transcription of CIITA from promoter III having been observed in unrelated melanoma cell lines, we propose the hypothesis that this phenomenon might not be a random event, but could be linked to the neoplasic state of the melanoma cells.