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- Title
MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.
- Authors
Shachaf, Catherine M.; Kopelman, Andrew M.; Arvanitis, Constadina; Karlsson, Åsa; Beer, Shelly; Mandl, Stefanie; Bachmann, Michael H.; Borowsky, Alexander D.; Ruebner, Boris; Cardiff, Robert D.; Qiwei Yang; Bishop, J. Michael; Contag, Christopher H.; Felsher, Dean W.
- Abstract
Hepato cellular carcinoma is generally refractory to clinical treatment'. Here, we report that inactivation of the MYC onco- gene 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 a-fetoprotein, the increase in expression of liver cell markers cytokeratin 8 and carcino- embryonic 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 tumor- igenesis 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 tumour dormancy.
- Subjects
LIVER cancer; CANCER cells; LIVER cells; TUMORS; PLURIPOTENTIAL theory (Mathematics); NONLINEAR theories
- Publication
Nature, 2004, Vol 431, Issue 7012, p1112
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature03043