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PMID: 19934271 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Bmi1 functions as an oncogene independent of Ink4A/Arf repression in hepatic carcinogenesis.

Molecular cancer research : MCR ·Vol. 7 ·No. 12 ·2009-12-00 ·Pages 1937-45

Xu CR, Lee S, Ho C, Bommi P, Huang SA, Cheung ST, Dimri GP, Chen X

Abstract

Bmi1 is a polycomb group proto-oncogene that has been implicated in multiple tumor types. However, its role in hepatocellular carcinoma (HCC) development has not been well studied. In this article, we report that Bmi1 is overexpressed in human HCC samples. When Bmi1 expression is knocked down in human HCC cell lines, it significantly inhibits cell proliferation and perturbs cell cycle regulation. To investigate the role of Bmi1 in promoting liver cancer development in vivo, we stably expressed Bmi1 and/or an activated form of Ras (RasV12) in mouse liver. We found that while Bmi1 or RasV12 alone is not sufficient to promote liver cancer development, coexpression of Bmi1 and RasV12 promotes HCC formation in mice. Tumors induced by Bmi1/RasV12 resemble human HCC by deregulation of genes involved in cell proliferation, apoptosis, and angiogenesis. Intriguingly, we found no evidence that Bmi1 regulates Ink4A/Arf expression in both in vitro and in vivo systems of liver tumor development. In summary, our study shows that Bmi1 can cooperate with other oncogenic signals to promote hepatic carcinogenesis in vivo. Yet Bmi1 functions independent of Ink4A/Arf repression in liver cancer development.

MeSH Terms
Animals Carcinoma, Hepatocellular/genetics,metabolism,pathology Cell Cycle Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase Inhibitor p16/genetics,metabolism Down-Regulation/genetics Enzyme Activation Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Hepatocytes/metabolism Humans Liver Neoplasms/genetics,metabolism,pathology Mice Nuclear Proteins/genetics,metabolism Polycomb Repressive Complex 1 Proto-Oncogene Mas Proto-Oncogene Proteins/genetics,metabolism RNA, Small Interfering/metabolism Repressor Proteins/genetics,metabolism Tumor Suppressor Protein p14ARF/genetics,metabolism Up-Regulation/genetics ras Proteins/metabolism
Chemicals
BMI1 protein, human Bmi1 protein, mouse Cyclin-Dependent Kinase Inhibitor p16 MAS1 protein, human Nuclear Proteins Proto-Oncogene Mas Proto-Oncogene Proteins RNA, Small Interfering Repressor Proteins Tumor Suppressor Protein p14ARF Polycomb Repressive Complex 1 ras Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Xu Chuan-Rui
Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA 94143, USA.
Lee Susie
Ho Coral
Bommi Prashant
Huang Shi-Ang
Cheung Siu Tim
Dimri Goberdhan P
Chen Xin
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Article Info
Journal
Molecular cancer research : MCR
Abbr.
Mol Cancer Res
ISSN
1557-3125
DOI
10.1158/1541-7786.MCR-09-0333
Published
2009-12-00
Epub
2009-00-24
Pages
1937-45
Language
English
Region
United States
NLM ID
101150042
PMCID
PMC2796287
Subset
IM
Grants
NIDDK NIH HHS · P30DK026743 · United States
NCI NIH HHS · R01CA136606 · United States
NCI NIH HHS · R21 CA131625 · United States
NIDDK NIH HHS · P30 DK026743 · United States
NCI NIH HHS · R01CA094150 · United States
NCI NIH HHS · R01 CA136606-01A2 · United States
NCI NIH HHS · R01 CA136606 · United States
NCI NIH HHS · R21CA131625 · United States
NCI NIH HHS · R21 CA131625-01A1 · United States
NCI NIH HHS · R01 CA094150 · United States
External Links
PubMed source DOI: 10.1158/1541-7786.MCR-09-0333 PMC Full Text View journal details
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