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Merlin protein found to control liver stem cells, prevent tumor development
Date:8/12/2010

A protein known to be involved in a rare hereditary cancer syndrome may have a role in the regulation of liver stem cells and the development of liver cancer. In the August 15 issue of Genes & Development, a Massachusetts General Hospital (MGH) research team describes finding that the protein called merlin, encoded by the NF2 (neurofibromatosis type 2) gene, controls the activity of adult stem cells that give rise to the two major types of liver cells.

"We found that mutation of the NF2 tumor suppressor gene in the mouse liver led to a dramatic overproliferation of liver stem cells the cells that contribute to the liver's remarkable ability to regenerate," says Andrea McClatchey, PhD, of the MGH Center for Cancer Research, who led the study. "These mice go on to develop the two forms of liver cancer that are most common in humans, suggesting that liver stem cells may be the cells of origin of these tumors."

The liver has a rare ability to regenerate and replace damaged or missing tissue. If one lobe is removed for transplantation, the rest of the donor's organ will return to its previous size and the transplanted lobe will grow to match the needs of the recipient. This regeneration usually involves proliferation of the most characteristic liver cells, called hepatocytes, and of bile duct cells; but if that growth is blocked or those cells are damaged, a population of less-differentiated progenitor cells will start to expand. These liver stem cells have been identified in rodents, and potential equivalents found but not confirmed in humans.

Previous research also indicated that liver stem cells may be the source of some tumors in animals, and suggested that the tumor suppressor gene NF2 may help prevent tumor development. Originally discovered through its involvement in the rare genetic disorder neurofibromatosis type 2, the NF2 gene codes for merlin, a protein known to suppress the activity of a number of cellular re
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Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert

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