connecN glioma cells and PKC place. As a critical connection point between the activation of mTOR EGFR relevance of Ren validating first astrocytoma, we analyzed samples Ren prim Ren human glioblastoma obtained by surgical resection before therapy. The abundance of EGFR in these samples at p RPS6 total PKC PKC p and p are correlated, but shows little correlation with the abundance of Akt p. Although the efficacy of erlotinib in patients with EGFR dependent-Dependent dependent and the status of PTEN, we thought that CCT239065 the inhibition of PKC should be effective, even in diplomacy EGFR PTENmt glioma, ar support for PKC inhibition as a therapeutic strategy commonly glioma. Were treated in accordance with this hypothesis, glioma cells with the PKC inhibitor showed up pan-indolyl maleimide I, the F Ability Lebensf Ngig independent Ngig EGFR or PTEN decreased. W W during erlotinib affects the abundance RPS6 p only in cells PTENwt, BIM I reduced substrate phosphorylation by PKC and mTOR and RPS6 substrate MARCKS in cells PTENmt PTENwt, although the effect of BIM I, p RPS6 in U373: EGFR cells was modest. BIM I treatment induced arrest of cells in the G1 and G2 PTENwt PTENmt, suggesting that the effect of this compound by inhibition of PKC rather T nonspecific toxicity Was t get t. DISCUSSION investigate the failure of EGFR inhibitors block the proliferation of glioma cells PTENmt, we investigated the signaling agent whose activation correlates with the effect of blockade of EGFR in tumor cell lines proliferation.
This concept more data than the phosphorylation of mTOR and its downstream targets were fixed S6K RPS6 biomarkers capacitance F t of EGFR inhibitors to block the proliferation of glioma cells. The F Ability of EGFR inhibitors block F Akt phosphorylation, but also correlated with response to treatment. Use St GAIN both gain Apixaban and loss of function tze years we have shown that the activity of t The law did not correlate with the activation or proliferation of mTOR. Instead, we have determined to be critical for PKC signaling between EGFR and mTOR in glioma two PTENwt. We pr Sentieren data from samples Rtumoren prims abundance of EGFR, PKC p and p RPS6 are aligned, but poorly correlated with the abundance of Law p. Finally, we show that pharmacological inhibition of PKC blocked proliferation PTENmt glioma, in which the inhibition of EGFR had no effect. Although inhibitor BIM I was not specific for PKC, this agent blocked the PKC substrate MARCKS p. In addition, BIM I PTENmt PTENwt induced G1 arrest in cells and G2 cells. If the antiproliferative effects of this compound were unspecific, then the cell cycle arrest induced by BIM, I should not dependent Ngig abh Dependent. The status of the PTEN What are the implications of these observations Gain Gain of the EGFR is a known compound with glioblastoma multiforme tumors. This observation, with a poor prognosis in this disease, in combination, wherein