Elevated levels of IL-1β in Fanconi Anemia group A patients due to a constitutively active PI3K-AKT pathway are capable of promoting tumor cell proliferation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical Journal Année : 2009

Elevated levels of IL-1β in Fanconi Anemia group A patients due to a constitutively active PI3K-AKT pathway are capable of promoting tumor cell proliferation

Ana Ibáñez
  • Fonction : Auteur
Paula Río
  • Fonction : Auteur
José Antonio Casado
  • Fonction : Auteur
Juan Antonio Bueren
  • Fonction : Auteur
José Luis Fernández-Luna
  • Fonction : Auteur

Résumé

Fanconi Anemia is a hereditary disease characterized by congenital malformations, progressive bone marrow failure and an extraordinary elevated predisposition to develop cancer. In the present article we describe an anomalous high level of the proinflammatory cytokine IL-1β present in the serum of Fanconi Anemia patients. The elevated levels of IL-1β were completely reverted by transduction of a wild type copy of the FancA cDNA into FA-A lymphocytes. Although the transcription factor NF-κB is a well established regulator of IL-1β expression, our experiments did not show any proof of elevated NF-κB activity in FA-A cells. However, we found that the overexpression of IL-1β in FA-A cells is related to a constitutively activated PI3K-AKT pathway in these cells. We provide evidence that the effect of AKT on IL-1β activation is mediated by the inhibition of GSK3β. Finally, our data indicate that the levels of IL-1β produced by FA-A lymphoblasts are enough to promote an activation of the cell cycle in primary glioblastoma progenitor cells. Together, these data demonstrate that the constitutive activation of the PI3K-AKT pathway in FA cells upregulates the expression of IL-1β through a NF-κB-independent mechanism and that this overproduction activates the proliferation of tumor cells.

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Dates et versions

hal-00479118 , version 1 (30-04-2010)

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Ana Ibáñez, Paula Río, José Antonio Casado, Juan Antonio Bueren, José Luis Fernández-Luna, et al.. Elevated levels of IL-1β in Fanconi Anemia group A patients due to a constitutively active PI3K-AKT pathway are capable of promoting tumor cell proliferation. Biochemical Journal, 2009, 422 (1), pp.161-170. ⟨10.1042/BJ20082118⟩. ⟨hal-00479118⟩

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