GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.

PloS One
Bart A WestermanMaarten van Lohuizen

Abstract

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 p16(INK4A)/Rb rather than on regulation of p19(ARF)/p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indica...Continue Reading

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Citations

Sep 3, 2013·Molecular and Cellular Endocrinology·Hugo Vankelecom, Jianghai Chen
Oct 16, 2013·Peptides·Richard J Bodnar
Sep 1, 2015·Molecular and Cellular Endocrinology·K E LinesR V Thakker
Jul 30, 2015·Endocrine-related Cancer·Katharina LampichlerSabina Baumgartner-Parzer
Aug 20, 2014·Frontiers in Oncology·David A CanoAlfonso Leal-Cerro
Nov 4, 2016·Transgenic Research·Martijn A J KoppensMaarten van Lohuizen
Dec 20, 2017·Frontiers in Endocrinology·Hugo Vankelecom, Heleen Roose
Feb 27, 2016·Cancer Science·Yoshihiro HayakawaTatsuro Irimura
Nov 30, 2016·Acta Neuropathologica Communications·Branavan ManoranjanSheila K Singh

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Methods Mentioned

BETA
transgenic
FACS
electron microscopy

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