在一种神经胶质瘤小鼠模型中，Bmi1以一种不依赖Ink4a/Arf的方式控制肿瘤发展。

Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma.

作者信息

Bruggeman Sophia W M, Hulsman Danielle, Tanger Ellen, Buckle Tessa, Blom Marleen, Zevenhoven John, van Tellingen Olaf, van Lohuizen Maarten

机构信息

Division of Molecular Genetics, The Netherlands Cancer Institute, 1066CX, Amsterdam, the Netherlands.

出版信息

Cancer Cell. 2007 Oct;12(4):328-41. doi: 10.1016/j.ccr.2007.08.032.

DOI:10.1016/j.ccr.2007.08.032

PMID:17936558

Abstract

The Polycomb group and oncogene Bmi1 is required for the proliferation of various differentiated cells and for the self-renewal of stem cells and leukemic cancer stem cells. Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects. However, we now demonstrate in an orthotopic transplantation model for glioma, a type of cancer harboring cancer stem cells, that Bmi1 is also required for tumor development in an Ink4a/Arf-independent manner. Tumors derived from Bmi1;Ink4a/Arf doubly deficient astrocytes or neural stem cells have a later time of onset and different histological grading. Moreover, in the absence of Ink4a/Arf, Bmi1-deficient cells and tumors display changes in differentiation capacity.

摘要

多梳蛋白家族成员及癌基因Bmi1对于各种分化细胞的增殖以及干细胞和白血病癌干细胞的自我更新是必需的。Ink4a/Arf基因座的抑制是一种已被充分描述的机制，通过该机制Bmi1可发挥其增殖作用。然而，我们现在在一种原位移植模型（一种含有癌干细胞的癌症类型）中证明，在胶质瘤中，Bmi1以一种不依赖Ink4a/Arf的方式对于肿瘤发生也是必需的。源自Bmi1和Ink4a/Arf双缺陷星形胶质细胞或神经干细胞的肿瘤具有较晚的发病时间和不同的组织学分级。此外，在没有Ink4a/Arf的情况下，Bmi1缺陷细胞和肿瘤表现出分化能力的变化。