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Stowers scientists clarify role of tumor suppressor gene

Kansas City, Mo. (April 24, 2006) Jiwang Zhang, Ph.D., formerly a Senior Research Associate at the Stowers Institute for Medical Research, and Linheng Li, Ph.D., Associate Investigator, are credited as the first and last authors, respectively, on a paper highlighting several previously unknown functions of phosphatase and tensin homolog (PTEN), an important tumor suppressor gene.

The findings, published on the Nature Web site on April 23, identified an intrinsic pathway involving PTEN that helps control the transitions that stem cells make between the quiescent and active states. The results demonstrate the importance of the intermediate 'activated' state that describes stem cells that are between the extremes of quiescence and rapid cycling. PTEN functions to decide whether to progress further though the cell cycle or return to a quiescent (G0) state. Disrupting PTEN in stem cells results in more active cycling and a loss of the quiescent pool of stems cells that is necessary for long-term stem cell maintenance.

PTEN can be phosphorylated in response to other signals that modulate its function. The Li Lab's work demonstrated distinct populations of hematopoetic stem cells (HSCs) with phosphorylated and unphosphorylated forms of PTEN, suggesting that PTEN phosphorylation may be a 'sensor' that could help integrate external cues with the HSC quiescence/activation switch.

"Although the primary mutation occurs in stem cells, leading to short-term expansion of normal stem cells, this mutation alone is not enough to support unlimited expansion of either normal or cancer stem cells," said Dr. Li. "A secondary mutation is therefore required to empower the leukemia cells resulting from this mutation to undergo unlimited expansion. Exploring the nature of the secondary mutation, together with the primary mutation in PTEN, can help to understand the self-renewal ability of stem cells and perhaps will identify new molecules that can be targeted to
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Contact: Marie Jennings
mfj@stowers-institute.org
816-926-4015
Stowers Institute for Medical Research
23-Apr-2006


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