论文部分内容阅读
Introduction: The mTOR (mammalian target of rapamycin) serine/threonine kinase is one of the key regulators of the cell cycle, growth and survival.mTOR abnormal regulation has been linked to both cancer cells survival and death.Recently, it is reported that aberrant activation ofmTOR pathway has been found in many hematological malignancies including AML.Moreover, it has been found that mTOR pathway is activated by several upstream proteins such as ckit and FLT3.However, FLT3 and ckit mutations are exclusive and account for up to about two third of AML patients.The dysregulated activity of these proteins can contribute to the aberrant activation of major cell survival or proliferation pathways such us mTOR pathway.Recent studies found that abnormalities in the cytokines network are involved in numerous types of leukemia.Up-regulated secretions of several cytokines among leukemia, especially AML patients have been reported.However, the effects of the cytokines on the mTOR signaling pathway molecules are still unclear.Deciphering and understanding the relationship among these molecules may uncover potential mechanisms which may have contributed to the pathogenesis of leukemic diseases.Aim: To determine the effects of various cytokines on mTOR signaling pathway related genes expression patterns.Methods: Kasumi-1 leukemia cell line was treated with different concentrations of various cytokines.Total RNA was isolated from both treated and non treated cell line.RT-PCR was used to determine the gene expression pattern.Results: Interestingly, this study showed that there were down-regulation of both mTOR and FLT3, down-regulation of both mTOR and ckit, down-regulation ofmTOR genes expression with the gradual increment of TNF-α, IFN-y and IL-1 α concentration respectively.On the other hand, there was up-regulation of mTOR gene expression with gradual increment of IL-3 concentration.However, the rest of the cytokines appear to have no effects on these genes.Conclusion: The results suggest that TNF-α, INF-y, IL-1α and IL-3 may play a role in the regulation of mTOR signaling pathway.