Document Detail

MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.
MedLine Citation:
PMID:  15475948     Owner:  NLM     Status:  MEDLINE    
Hepatocellular carcinoma is generally refractory to clinical treatment. Here, we report that inactivation of the MYC oncogene is sufficient to induce sustained regression of invasive liver cancers. MYC inactivation resulted en masse in tumour cells differentiating into hepatocytes and biliary cells forming bile duct structures, and this was associated with rapid loss of expression of the tumour marker alpha-fetoprotein, the increase in expression of liver cell markers cytokeratin 8 and carcinoembryonic antigen, and in some cells the liver stem cell marker cytokeratin 19. Using in vivo bioluminescence imaging we found that many of these tumour cells remained dormant as long as MYC remain inactivated; however, MYC reactivation immediately restored their neoplastic features. Using array comparative genomic hybridization we confirmed that these dormant liver cells and the restored tumour retained the identical molecular signature and hence were clonally derived from the tumour cells. Our results show how oncogene inactivation may reverse tumorigenesis in the most clinically difficult cancers. Oncogene inactivation uncovers the pluripotent capacity of tumours to differentiate into normal cellular lineages and tissue structures, while retaining their latent potential to become cancerous, and hence existing in a state of tumour dormancy.
Catherine M Shachaf; Andrew M Kopelman; Constadina Arvanitis; Asa Karlsson; Shelly Beer; Stefanie Mandl; Michael H Bachmann; Alexander D Borowsky; Boris Ruebner; Robert D Cardiff; Qiwei Yang; J Michael Bishop; Christopher H Contag; Dean W Felsher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-10-10
Journal Detail:
Title:  Nature     Volume:  431     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-28     Completed Date:  2004-11-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  1112-7     Citation Subset:  IM    
Division of Medical Oncology, Department of Medicine, Stanford University, California 94305, USA.
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MeSH Terms
Bile Ducts / cytology,  metabolism
Carcinoma, Hepatocellular / genetics*,  metabolism,  pathology*,  therapy
Cell Differentiation*
Cell Transformation, Neoplastic
Gene Expression Regulation, Neoplastic
Genes, myc / genetics*
Luminescent Measurements
Mice, SCID
Mice, Transgenic
Proto-Oncogene Proteins c-myc / genetics,  metabolism
Stem Cells / cytology,  metabolism
Tumor Markers, Biological / analysis
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myc; 0/Tumor Markers, Biological

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