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Regulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRA

meijin 添加于 2012/3/21 13:17:16  1157次阅读 | 0次推荐 | 0个评论

Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial early event in neuroblastoma pathogenesis is arrested differentiation of neuroblasts at various stages. Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation of neuroblastoma cells. However, the signaling pathways that are involved in this process remain largely unknown. Here, we report that inhibition of endogenous FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct its basal mRNA expression as well as its induction upon serum deprivation. Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic expression of PDGFRA abolished the blockage of neuroblastoma differentiation by FOXOs inhibition. These findings define the FOXO–PDGFRA axis as crucial mechanistic components that govern TPA-induced neuroblastoma differentiation.

作 者:Mei, Yang; Wang, Zhanxiang; Zhang, Lei; Zhang, Yiru; Li, Xiaoyu; Liu, Huihui; Ye, Jing; You, Han
期刊名称: Proceedings of the National Academy of Sciences
期卷页: 第卷 第期 ~页
学科领域:医学科学 » 肿瘤学 » 肿瘤遗传
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原文链接:http://www.pnas.org/content/early/2012/03/08/1119535109.abstract
DOI: 10.1073/pnas.1119535109
ISBN: 0027-8424
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相关报道: http://paper.sciencenet.cn/htmlpaper/201232113281194223136.shtm
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