NEW YORK (Reuters Health) - In mice, inactivation of the MYC oncogene induces sustained regression of invasive hepatocellular carcinoma, scientists from California report in an online issue of the journal Nature released Sunday.
In a telephone interview with Reuters Health, Dr. Dean W. Felsher from Stanford University said targeted MYC inactivation might be an effective treatment strategy for liver cancer, which is generally refractory to existing therapies.
The MYC oncogene is one of the most commonly activated oncogenes associated with the pathogenesis of liver tumors. In transgenic mice expressing human MYC in liver cancer cells, Dr. Felsher’s team found that shutting off MYC turns liver cancer cells into normal liver cells capable of differentiation.
“MYC inactivation resulted en masse in tumor cells differentiating into hepatocytes and biliary cells forming bile duct structures, and this was associated with rapid loss of expression of the tumor 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,” they report.
MYC reactivation promptly restores the neoplastic potential of these cells and some of them revert back to being cancerous.
“This study shows that we can reverse the process of cancer by shutting off cancer genes, but sometimes some of those cells even when they look normal retain the capacity to be cancer cells,” Dr. Felsher said.
“This is important,” he added, “because most of the time we as doctors decide that we’ve succeeded in treating the cancer by looking to see if the tumor is gone. Maybe part of the reason why therapies sometimes fail is not because some of the cells are not being eliminated but because some of the cells look like they become normal and then revert back to being cancer cells,” he theorized.
Dr. Felsher’s team is now trying to figure out precisely what cells can become malignant again. “If we knew that then hopefully we could come up with a better therapy,” he said.
The current study builds on previous work by the same researchers showing that MYC inactivation causes osteogenic sarcoma cells to differentiate into mature osteocytes. It is noteworthy that in this earlier study, when MYC was reactivated the cells did not become cancerous again, but underwent apoptosis instead. (See Reuters Health report July 5, 2002).
Source: Nature 2004. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Phenomena, Cell Phenomena, and Immunity: Biological Sciences: Biology: Cell Differentiation: Cell Physiology: Disease Models, Animal: DNA-Binding Proteins: Gene Expression Regulation: Genetics: Genetics, Biochemical: Growth and Embryonic Development: Molecular Biology: Nuclear Proteins: Physiological Processes: Proto-Oncogene Proteins: Proto-Oncogene Proteins c-myc: Gene Silencing: Biological Sciences: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
