Unknown,Transcriptomics,Genomics,Proteomics

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MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer

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. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Using regression correlation

ORGANISM(S): Mus musculus

SUBMITTER: Asa Karlsson

PROVIDER: E-GEOD-3018 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.

Shachaf Catherine M CM Kopelman Andrew M AM Arvanitis Constadina C Karlsson Asa A Beer Shelly S Mandl Stefanie S Bachmann Michael H MH Borowsky Alexander D AD Ruebner Boris B Cardiff Robert D RD Yang Qiwei Q Bishop J Michael JM Contag Christopher H CH Felsher Dean W DW

Nature 20041010 7012

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 carcinoem ...[more]

PMID: 15475948

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MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer

Publications

MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.

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