Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon-induced apoptosis
Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon-induced apoptosis
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DOI：
10.1111/1346-8138.12160
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发表时间：
2013-08-01
影响因子：
3.1
通讯作者：
Tu, Ping
中科院分区：
文献类型：
--
作者：
Gu, Xiaoguang;Wang, Yang;Tu, Ping
BCL11B 是一种 Kruppel 样 C2H2 型锌指转录因子，与多种人类恶性肿瘤有关。最近的证据表明，过度表达的 BCL11B 赋予恶性细胞化疗耐药性，而抑制 BCL11B 会导致细胞凋亡增加，这表明其与皮肤细胞淋巴瘤 (C) 具有潜在的致病相关性，其特点是对化疗诱导的细胞凋亡具有抵抗力。分别采用定量逆转录聚合酶链反应和免疫组织化学方法比较BCL11B在蕈样肉芽肿（MF）不同阶段和良性炎症性皮肤病（BID）不同阶段的mRNA和蛋白表达情况。与 BID 相比，BCL11B 在 MF 的所有阶段中 mRNA 表达水平和蛋白质水平均表现出显着上调。此外，BCL11B 表达随着病变肿瘤分期和总体疾病分期的进展而增加。此外，为了评估C定向处理下BCL11B的动态表达，在干扰素(IFN)--2b和甲氨蝶呤处理C细胞系Hut78细胞后评估BCL11B表达和细胞凋亡。 IFN--2b（而非甲氨蝶呤）诱导 BCL11B 抑制和细胞凋亡，表明 BCL11B 可能在 IFN--2b 的抗 C 作用中发挥重要作用。总之，我们的研究证明了 MF 病变中 BCL11B 的过度表达及其与疾病进展的潜在相关性。此外，我们还提供了 BCL11B 抑制方法作为针对晚期 MF 化疗耐药肿瘤细胞的潜在治疗方法的证据。
BCL11B is a Kruppel-like C2H2-type zinc finger transcription factor, which has been associated with several human malignancies. Recent evidence showed that overexpressed BCL11B conferred chemoresistance to malignant cells and that inhibiting BCL11B led to increased apoptosis, suggesting its potential pathogenic relevance in cutaneous -cell lymphomas (C ), which were characterized by the resistance to chemotherapy-induced apoptosis. BCL11B in different stages of mycosis fungoides (MF), quantitative reverse transcription polymerase chain reaction and immunohistochemistry were performed to compare the mRNA and protein expression among different stages of MF and benign inflammatory dermatoses (BID), respectively. BCL11B demonstrated significant upregulation in all stages of MF, compared with BID, in both mRNA expression level and protein level. In addition, BCL11B expression increased with advancing lesion tumor stage and overall disease stage. Further, to evaluate the dynamic expression of BCL11B under C -directed treatment, BCL11B expression and cell apoptosis were evaluated after interferon (IFN)--2b and methotrexate treatment on C cell line Hut78 cells. IFN--2b, but not methotrexate, induced BCL11B inhibition and cell apoptosis, suggesting that BCL11B may play important roles in the anti-C effect of IFN--2b. In conclusion, our study demonstrated the overexpression of BCL11B in MF lesions and its potential relevance to disease progression. In addition, we provided evidence for BCL11B inhibitory approaches as a potential treatment to target chemoresistant tumor cells in advanced MF.