定义导致 hedgehog 信号通路在弥漫性大 B 细胞淋巴瘤中激活的因素。
Defining causative factors contributing in the activation of hedgehog signaling in diffuse large B-cell lymphoma.
机构信息
Molecular Genetic Technology Program, School of Health Sciences, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Leuk Res. 2012 Oct;36(10):1267-73. doi: 10.1016/j.leukres.2012.06.014. Epub 2012 Jul 17.
Abstract
Hedgehog (Hh) signaling pathway is activated in diffuse large B-cell lymphoma (DLBCL). Genetic abnormalities that explain activation of Hh signaling in DLBCL are unknown. We investigate the presence of amplifications of Hh genes that might result in activation of this pathway in DLBCL. Our data showed few extra copies of GLI1 and SMO due to chromosomal aneuploidies in a subset of DLBCL cell lines. We also showed that pharmacologic inhibition of PI3K/AKT and NF-κB pathways resulted in decreased expression of GLI1 and Hh ligands. In conclusion, our data support the hypothesis that aberrant activation of Hh signaling in DLBCL mainly results from integration of deregulated oncogenic signaling inputs converging into Hh signaling.
摘要
Hedgehog (Hh) 信号通路在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中被激活。目前尚不清楚哪些遗传异常导致了 DLBCL 中 Hh 信号的激活。我们研究了是否存在 Hh 基因的扩增，这些扩增可能导致该通路在 DLBCL 中的激活。我们的数据显示，由于亚组的 DLBCL 细胞系中存在染色体非整倍性，导致 GLI1 和 SMO 的少数额外拷贝。我们还表明，PI3K/AKT 和 NF-κB 通路的药理学抑制导致 GLI1 和 Hh 配体的表达降低。总之，我们的数据支持这样一种假说，即 DLBCL 中 Hh 信号的异常激活主要是由于失调的致癌信号输入整合到 Hh 信号中而导致的。
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