Gene Linked to Tumor-Like Properties of Brain Stem Cells
Loss of PTEN gene promotes self-renewal and entry into the cell division cycle
FRIDAY, Dec. 23 (HealthDay News) -- Genetically engineered mice that lack a key tumor suppressor gene have neural stem cells that self-renew and act like tumor cells when grown in culture, according to a study published online Dec. 22 in the Proceedings of the National Academy of Sciences Early Edition. The findings suggest that loss of the tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) allows cells to take an important first step in the path to tumorigenesis.
Harley I. Kornblum, M.D., Ph.D., and colleagues from the University of California, Los Angeles, purified neural stem cells from either normal mice or mice missing the PTEN gene. This gene is often mutated in glioblastomas, the researchers note, and the PTEN-deficient mice were previously found to have substantially larger brains.
In contrast to normal stem cells, the PTEN-deficient neural stem cells retained the ability to self-renew, grew more rapidly, and retained the ability to differentiate into neural or glial cells. The PTEN-deficient neural stem cells were also able to exit the resting phase of the cell division cycle more easily and showed less dependence on growth factors for survival.
"Taken together, these data suggest that the loss of PTEN confers an increased self-renewal capacity to neural stem/progenitor cells, a potentially important mechanism for brain tumorigenesis," Kornblum and colleagues conclude.