EGFR-dependent and independent activation of Akt/mTOR cascade in bone and soft tissue tumors

摘要: To gain the insight into involvement of signaling mediated by mammalian target rapamycin (mTOR) in phenotype and biological profiles tumors tumor-like lesions bone soft tissue, we analyzed expression phosphorylation (activation) mTOR its correlation with status upstream downstream modulator proteins Akt, p70S6-kinase (S6K), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which refer to collectively as cassette proteins. Immunohistochemical analysis 140 cases showed activation Akt 55% (61% malignant 27% benign), 61% (66% 39% benign). The preponderance was found peripheral nerve sheath (malignant tumor schwannoma), skeletal muscle origin (rhabdomyosarcoma), those exhibiting epithelial nature (chordoma synovial sarcoma). Together result immunoblotting analysis, it shown that many particular exhibited S6K, 4E-BP1, suggesting constitutive Akt/mTOR pathway. In addition, although pathway largely independent epidermal growth receptor (EGFR), mutation EGFR frequently accompanied Akt-mTOR-S6K/4E-BP1. By clinicopathological correlates statistically higher probability metastasis. We conclude mTOR-mediated function not only proliferation cells, but also differentiation and/or maintenance morphological phenotypes rhabdomyoblastic cell origin. Furthermore, may modulate morphogenesis nature. Additionally, activated have a Overall, these results suggest inhibitors be useful novel components combined chemotherapy for defined subset tissue sarcomas.