Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer
Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer
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DOI：
10.1038/onc.2012.175
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发表时间：
2013-03-21
期刊：
影响因子：
8
通讯作者：
Massoumi, R.
中科院分区：
文献类型：
--
作者：
Ahlqvist, K.;Saamarthy, K.;Massoumi, R.
B细胞白血病3（B-cell leukemia 3，Bcl-3）是κ B抑制因子家族的一员，通过转录激活因子或靶基因的抑制因子来调节多种生物学过程。由于在不同类型的人类癌症中检测到高水平的Bcl-3表达和活化，Bcl-3已被标记为原癌基因。我们的研究揭示了Bcl-3在人前列腺癌（PCa）中的表达显著上调，其中观察到炎性细胞浸润。PCa中Bcl-3表达升高依赖于促炎细胞因子白细胞介素-6介导的STAT 3激活。微阵列分析，在PCa细胞中使用Bcl-3敲低，确定螺旋-环-螺旋蛋白的DNA结合（Id）家族的抑制剂作为潜在的Bcl-3调节基因。Bcl-3基因敲低降低了Id-1和Id-2蛋白的丰度，并促进PCa细胞在抗癌药物治疗后更容易发生凋亡。我们的数据表明，Bcl-3的失活可能会导致敏感的癌细胞化疗药物诱导的凋亡，从而表明在PCa治疗的潜在治疗策略。Oncogene（2013）32，1601-1608; doi：10.1038/onc.2012.175; 2012年5月14日在线发表
B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of kappa B family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. As high levels of Bcl-3 expression and activation have been detected in different types of human cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA-binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and boosted PCa cells to be more receptive to undergoing apoptosis following treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis, thus suggesting a potential therapeutic strategy in PCa treatment. Oncogene (2013) 32, 1601-1608; doi:10.1038/onc.2012.175; published online 14 May 2012