Research Article

Conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST

Figure 4

Expression microarray analysis of PTEN and EGFR in human peripheral nerve tumors. (a) Purified human Schwann cells from normal sciatic nerve (N-SC), dermal neurofibroma cell lines (dNF-SC), and plexiform neurofibroma cell lines (pNF-SC). Transformed cells from malignant peripheral nerve sheath cell lines (MPNST-C). Asterisks indicate sporadic MPNST samples. (b) Solid dermal neurofibromas (dNF), plexiform neurofibromas (pNF), and malignant peripheral nerve sheath tumors (MPNST). Four different probes for EGFR were used. Red, increase in red intensity as expression increases; Blue, increase in blue intensity as expression decreases. (c) Conditional inactivation of Pten and EGFR overexpression in Schwann cells resulted in high-grade PNST initiation and/or progression due to the upregulation of both Ras/Mapk/Erk and Pi3k/Akt/mTor signaling pathways (right). Inactivation of Pten alone resulted in reduced latency with low-grade PNST tumorigenesis at low penetrance (middle). Conditional inactivation of Pten alone can result in low-grade PNST tumorigenesis via the upregulation of the Pi3k/Akt/mTor signaling pathway. Partial conditional inactivation of Pten in the context of EGFR overexpression in Schwann cells resulted in prolonged latency with hyperplasia to low-grade PNST tumorigenesis at low penetrance (left), resulting in upregulation of Ras/Mapk/Erk and slight upregulation of the Pi3k/Akt/mTor signaling pathways. SOS1: son of sevenless homolog 1; GRB2: growth factor receptor-bound protein 2; IRS2: insulin receptor substrate 2; Dhh-Cre; ; EGFR ( Pten/C-EGFR), Dhh-Cre; ; EGFR (Pten-het/C-EGFR) and Dhh-Cre; ( Pten) animals.
620834.fig.004a
(a)
620834.fig.004b
(b)
620834.fig.004c
(c)