N, both anf Accessible and R788 Fostamatinib in response to treatment. We found that the constitutive activation of Akt is a pr Predictor of the sensitivity of the cells with the st Strongest cells with very low basal phosphorylation of S473 and T308. Tested after treatment with temsirolimus, a compensatory increase in the phosphorylation of Akt at both sites in the most sensitive endometrial cancer cell lines was detected, but especially the resistant cells showed no Akt phosphorylation at both sites, and some other resistant line, Hec50co showed a reduced phosphorylation. Thus, unlike sensitive cells, especially the resistant cells respond to a low basal phosphorylation of Akt, rather than compensatory hyper-phosphorylation after treatment, temsirolimus.
Interestingly, phospho PDK1, the kinase and Akt phosphorylation at T308, and lower in several resistant cell lines such as Hec1A and KLE. This is the best show, Civil Engineering of prime Ren cells and a general lack of dependence Dependence of the Akt signaling pathway to proliferation. In addition, the finding of compensatory activation of Akt in sensitive cells in accordance PD184352 with previous reports in the literature mTOR and PI3 kinase inhibitor Synergy second October 2011 | Volume 6 | Issue 10 | e26343 rapalog of Akt phosphorylation induced by various cancer cell lines, xenograft models of human tumors and patients. Compensatory hyper-phosphorylation of Akt schl Gt a potential mechanism by which cells initially Highest sensitive to escape the growth inhibitory effects of the drug and, secondly, have become resistant.
From these data we may use the between prime Ren resistance differ to a lack of basic act against dependence Dependence acquired resistance of hyper-Akt activation demonstrated in response to temsirolimus. Figure 1 Temsirolimus regulates fa Is differential Lebensf Ability of the cells and the phosphorylation of Akt in a dose-dependent Ngigen way. A, B, were Geb Rmutterschleimhautkrebszellen treated with increasing doses of temsirolimus for 72 hours. The results are a sensitivity or resistance by the Lebensf Ability of the cells determined separately. C, D, the phosphorylation of Akt and RS6 was determined after treatment with indicated doses of temsirolimus for 72 hours in the temsirolimus-sensitive or resistant cells by Western blot temsirolimus. Akt protein expression and RS6 total load is controlled Them.
doi: Synergy 10.1371/journal.pone.0026343.g001 mTOR and PI3-kinase inhibitor third October 2011 | Volume 6 | Issue 10 | e26343 fundamental expression of PTEN as a correlation with the activation of Akt, and cancer-early susceptibility of primary endometrial Ren 30%, 83% of PTEN mutations or loss of PTEN expression: is often the loss of PTEN function accompanied. The loss of tumor suppressor PTEN has been proposed to correlate sensitive to mTOR inhibitors in some other cancer cell lines and tumors of patients. As discussed above, Figures 1 and 2 show the presence of phospho basal act in some rows of buildings Rmutterschleimhautkrebszellen we suggest, is a marker for anf Ngliche sensibility T for temsirolimus monotherapy with compensatory hyper-phosphorylation as a marker for the acquired resistance . develop To understand the fundamental basis for high phosphorylation of Akt, we compared the expression of PTEN and Akt phospho-eight endometrial cancer cell lines based. As shown in Figure 2, five cell lines showed a loss of PTEN and three cells