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Publication : Susceptible stages in Schwann cells for NF1-associated plexiform neurofibroma development.

First Author  Le LQ Year  2011
Journal  Cancer Res Volume  71
Issue  13 Pages  4686-95
PubMed ID  21551250 Mgi Jnum  J:173624
Mgi Id  MGI:5049812 Doi  10.1158/0008-5472.CAN-10-4577
Citation  Le LQ, et al. (2011) Susceptible Stages in Schwann Cells for NF1-Associated Plexiform Neurofibroma Development. Cancer Res 71(13):4686-95
abstractText  Stem cells are under strict regulation by both intrinsic factors and the microenvironment. There is increasing evidence that many cancers initiate through acquisition of genetic mutations (loss of intrinsic control) in stem cells or their progenitors, followed by alterations of the surrounding microenvironment (loss of extrinsic control). In neurofibromatosis type 1 (NF1), deregulation of Ras signaling results in development of multiple neurofibromas, complex tumors of the peripheral nerves. Neurofibromas arise from the Schwann cell lineage following loss of function at the NF1 locus, which initiates a cascade of interactions with other cell types in the microenvironment and additional cell autonomous modifications. In this study, we sought to identify whether a temporal 'window of opportunity' exists during which cells of the Schwann cell lineage can give rise to neurofibromas following loss of NF1. We showed that acute loss of NF1 in both embryonic and adult Schwann cells can lead to neurofibroma formation. However, the embryonic period when Schwann cell precursors and immature Schwann cells are most abundant coincides with enhanced susceptibility to plexiform neurofibroma tumorigenesis. This model has important implications for understanding early cellular events that dictate neurofibroma development, as well as for the development of novel therapies targeting these tumors. Cancer Res; 71(13); 4686-95. (c)2011 AACR.
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