Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism

Filip Bednar, Heather K. Schofield, Meredith A. Collins, Wei Yan, Yaqing Zhang, Nikhil Shyam, Jaime A. Eberle, Luciana L. Almada, Kenneth P. Olive, Nabeel Bardeesy, Martin E. Fernandez-Zapico, Daisuke Nakada, Diane M. Simeone, Sean J. Morrison, Marina Pasca di Magliano

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Epigenetic dysregulation is involved in the initiation and progression of many epithelial cancers. BMI1, a component of the polycomb protein family, plays a key role in these processes by controlling the histone ubiquitination and long-term repression of multiple genomic loci. BMI1 has previously been implicated in pancreatic homeostasis and the function of pancreatic cancer stem cells. However, no work has yet addressed its role in the early stages of pancreatic cancer development. Here, we show that BMI1 is required for the initiation of murine pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination with a KrasG12D-driven pancreatic cancer mouse model. We also demonstrate that the requirement for Bmi1 in pancreatic carcinogenesis is independent of the Ink4a/Arf locus and at least partially mediated by dysregulation of reactive oxygen species. Our data provide new evidence of the importance of this epigenetic regulator in the genesis of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalCarcinogenesis
Volume36
Issue number7
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Cancer Research

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    Bednar, F., Schofield, H. K., Collins, M. A., Yan, W., Zhang, Y., Shyam, N., Eberle, J. A., Almada, L. L., Olive, K. P., Bardeesy, N., Fernandez-Zapico, M. E., Nakada, D., Simeone, D. M., Morrison, S. J., & di Magliano, M. P. (2015). Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism. Carcinogenesis, 36(7), 730-738. https://doi.org/10.1093/carcin/bgv058