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

doi:10.1093/carcin/bgv058

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

Oncology

Research output: Contribution to journal › Article › peer-review

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 Kras^G12D-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 language	English (US)
Pages (from-to)	730-738
Number of pages	9
Journal	Carcinogenesis
Volume	36
Issue number	7
DOIs	https://doi.org/10.1093/carcin/bgv058
State	Published - Jul 2015

ASJC Scopus subject areas

Cancer Research

Access to Document

10.1093/carcin/bgv058

Cite this

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

Bednar, F, Schofield, HK, Collins, MA, Yan, W, Zhang, Y, Shyam, N, Eberle, JA, Almada, LL, Olive, KP, Bardeesy, N, Fernandez-Zapico, ME, Nakada, D, Simeone, DM, Morrison, SJ & di Magliano, MP 2015, 'Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism', Carcinogenesis, vol. 36, no. 7, pp. 730-738. https://doi.org/10.1093/carcin/bgv058

@article{54937ff27eb14e26a18094cfa7d8fa23,

title = "Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism",

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.",

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

year = "2015",

month = jul,

doi = "10.1093/carcin/bgv058",

language = "English (US)",

volume = "36",

pages = "730--738",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

T1 - Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism

AU - Bednar, Filip

AU - Schofield, Heather K.

AU - Collins, Meredith A.

AU - Yan, Wei

AU - Zhang, Yaqing

AU - Shyam, Nikhil

AU - Eberle, Jaime A.

AU - Almada, Luciana L.

AU - Olive, Kenneth P.

AU - Bardeesy, Nabeel

AU - Fernandez-Zapico, Martin E.

AU - Nakada, Daisuke

AU - Simeone, Diane M.

AU - Morrison, Sean J.

AU - di Magliano, Marina Pasca

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84941657530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941657530&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgv058

DO - 10.1093/carcin/bgv058

M3 - Article

C2 - 25939753

AN - SCOPUS:84941657530

SN - 0143-3334

VL - 36

SP - 730

EP - 738

JO - Carcinogenesis

JF - Carcinogenesis

IS - 7

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this