MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-10

AUTHORS

Catherine M. Shachaf, Andrew M. Kopelman, Constadina Arvanitis, Åsa 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

ABSTRACT

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. More... »

PAGES

1112

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature03043

DOI

http://dx.doi.org/10.1038/nature03043

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008158389

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15475948


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature03043'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature03043'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature03043'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature03043'


 

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