Abstract
Differentiation of primary human vestibular nerve schwannomas (VS) caused by mutations of the NF2 gene was evaluated by examining the expression patterns of genes that are specifically expressed in different stages of Schwann cell lineage. In schwannoma cells that are not in contact with an axon, the expression levels of the major myelin sheath proteins, such as protein zero glycoprotein (P0), myelin basic protein (MBP), and peripheral myelin protein 22 (PMP22), were greatly reduced. However, high expression levels of nerve growth factor receptor (NGFR), neural cell adhesion molecule (N-CAM), and cell adhesion molecule L1 (L1) were observed. In addition, expression of transcription factors Krox20, Krox24, and SCIP/Oct6 was also detected in the tumor cells. These results suggest that loss of the NF2 gene was responsible for the transformation of the Schwann cells into a neoplastic stage that has a similar genetic profile to the pro-myelinating stage. Finally, the primary human vestibular schwannoma cells failed to be regulated and redifferentiated by a regenerating axon, when the human tumors were transplanted into sciatic nerve of nude rat. These results suggest that the NF2 gene might be involved in the differentiation of Schwann cells.
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