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GFAP-Cre-Mediated Transgenic Activation of Bmi1 Results in Pituitary Tumors
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文献简介

出版社:PLoS ONE

作者:Bart A. Westerman1,2 , Marleen Blom1 , Ellen Tanger 1 , Martin van der Valk3 , Ji-Ying Song3 , Marije van Santen4 , Jules Gadiot 1 , Paulien Cornelissen-Steijger 1 , John Zevenhoven1 , Haydn M. Prosser 5 , Anthony Uren1,6 , Eleonora Aronica7 , Maarten van Lohuizen1,8 *

编号:10.1371/journal.pone.0035943

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年份:2012点击量:610

文献摘要

        Bmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has been described to result in tumor inhibitory effects partly through INK4A/Arf mediated senescence and apoptosis and also through INK4A/Arf independent effects, it has not been proven that Bmi1 can be causally involved in the formation of these tumors. To see whether this is the case, we developed two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression in neural and glial lineages. We show here that these mice generate intermediate and anterior lobe pituitary tumors that are positive for ACTH and beta-endorphin. Combined transgenic expression of Bmi1 together with conditional loss of Rb resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi1 depends on regulation of p16INK4A /Rb rather than on regulation of p19ARF /p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indicates that Bmi1 could be causally involved in formation of these tumors similarly as in our mouse model.

 

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