【文章名】Elevated levels of IL-1 beta in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation
Elevated levels of IL-1 beta in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation
[摘要]：FA (Fanconi anaemia) is a hereditary disease characterized by congenital malformations, progressive bone marrow failure and an extraordinary elevated predisposition to develop cancer. In the present manuscript we describe an anomalous high level of the proinflammatory cytokine IL-1 beta (interleukin-1 beta) present in the serum of FA patients. The elevated levels of IL-1 beta were completely reverted by transduction of a wild-type copy of the FancA cDNA into FA-A (FA group A) lymphocytes. Although the transcription factor NF-kappa B (nuclear factor-kappa B) is a well established regullator of IL-1 beta expression, our experiments did not show any proof of elevated NF-kappa B activity in FA-A cells. However, we found that the overexpression of Ill in FA-A cells is related to a constitutively activated PI3K (phosphoinositide 3-kinase)-Akt pathway in these cells. We provide evidence that the effect of Akt on IL-1 beta activation is mediated by the inhibition of GSK3 beta (glycogen synthase kinase 3 beta). Finally, our data indicate that the levels of IL-1 beta produced by FA-A lymphoblasts are enough to promote an activation of the cell cycle in primary glioblastoma progenitor cells. Together. these results demonstrate that the constitutive activation of the PI3K-Akt pathway in FA cells upregulates the expression of IL-1 beta through all NF-kappa B independent mechanism and that this overproduction activates the proliferation of tumor cells.
