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髓母细胞瘤细胞系中Wnt信号通路的分子特征及β-连环蛋白过表达的功能

Molecular characterization of Wnt pathway and function of β-catenin overexpression in medulloblastoma cell lines.

作者信息

Geron Lenisa, Salomão Karina Bezerra, Borges Kleiton Silva, Andrade Augusto Faria, Corrêa Carolina Alves Pereira, Scrideli Carlos Alberto, Tone Luiz Gonzaga

机构信息

Department of Genetics, Ribeirão Preto Medical School, University of São Paulo - USP, 3900 Bandeirantes Avenue, Ribeirão Preto, SP, 14049-900, Brazil.

Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, Ribeirão Preto - SP, 14049-900, Brazil.

出版信息

Cytotechnology. 2018 Dec;70(6):1713-1722. doi: 10.1007/s10616-018-0260-2. Epub 2018 Oct 29.

Abstract

Medulloblastoma (MB) is the most common malignant childhood brain tumor. MB is currently classified into four molecular subgroups (Wnt, Shh, Group 3, and Group 4). The wingless (Wnt) pathway is responsible for embryonic development and is deregulated in MB. We analyzed the activation of the Wnt pathway in MB cell lines and its correlation with the Shh pathway, with emphasis on the importance of cellular characterization. Transient β-catenin transfection led to an increase in the β-catenin gene and protein expression in MB cell lines. Wnt pathway activation resulted in a reduced number of colonies in all cell lines studied and a significant increase in the G2/M cell cycle phase only in ONS-76 cells. Regarding the Shh pathway, transfection caused a reduced expression of the PTCH1 and SMO genes only in the UW473 cells. Further studies are needed to understand the mechanism underlying the molecular events associated with the effects of Wnt activation in MB.

摘要

髓母细胞瘤(MB)是儿童期最常见的恶性脑肿瘤。MB目前被分为四个分子亚组(Wnt、Shh、3组和4组)。无翅(Wnt)信号通路负责胚胎发育,在MB中失调。我们分析了MB细胞系中Wnt信号通路的激活情况及其与Shh信号通路的相关性,重点关注细胞特征的重要性。瞬时β-连环蛋白转染导致MB细胞系中β-连环蛋白基因和蛋白表达增加。Wnt信号通路激活导致所有研究的细胞系中集落数量减少,且仅在ONS-76细胞中G2/M细胞周期期显著增加。关于Shh信号通路,转染仅导致UW473细胞中PTCH1和SMO基因表达降低。需要进一步研究以了解与MB中Wnt激活效应相关的分子事件背后的机制。

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