In BRAF Mutant melanoma cells, inhibition of BRAF inhibitors with low molecular weight and siRNA knockdown leads to the induction of apoptosis by a mechanism that is obtained, the phosphorylation of Ser 75 BAD decreased, upregulation BMS-754807 BMF and Hte expression BIM. The identification of BIM as a key mediator, has regulated apoptotic PTEN mutated BRAF melanoma cells elucidated a novel mechanism of intrinsic resistance Rt be, by the Akt activation paradoxical PTEN 0 cells leads to remove the trailer Ufung of nuclear and reduced FOXO3a mRNA BIM . Potential clinical relevance, it was found that the dual inhibition of both BRAF and PI3K restored FOXO3a nuclear accumulation BIM upregulated expression at the mRNA and protein, and increased Ht the degree of apoptosis.
Similar results were also observed Saracatinib in melanoma cells intrinsically resistant to the MEK inhibitor AZD6244, where sensitivity could be restored by dual inhibition of both MEK and IGF1R, mTORC1 / 2 and AKT. Zus USEFUL support for the r Akt signaling in resistance to the BRAF inhibitor intrinsic were other studies that show that the. Overexpression of an active form of AKT3 prevented apoptosis in melanoma cells when BRAF V600E BRAF mutant was locked The use of LC MRM allows the expression level of BIM as a factor PTEN dependent-Dependent apoptosis mediated by identified BRAF inhibitor. If it were not for the exquisite sensitivity of the LC-MRM method and the F Ability to quantify accurately the levels of peptides that dependence Dependence of expression of PTEN has not been completed in the BIM process.
The usefulness and value of MRM LC is mainly because the k experiments Can evaluate the complexity of more t and details of biological processes in various human diseases. Current and projected value of future potential protein sequences LC MRM quantitative mass spectrometry quantification, especially LCMRM t appears as an alternative to antique Rpern based method for the detection and quantification of proteins. The development of peptide-based tests for protein expression, modification and even mutations k Implementations can be very fast. The selection of the target peptide sequence or existing tandem mass spectrometry data or LC MRM candidate screening peptide synthesis of stable isotope labeled standards, and analysis to the fit between the study elution and fragmentation patterns of endogenous peptide-standard and can be completed in a few days.
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