Role of PI3K signalling pathway in modulating hypoxia response in neuroblastoma


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Esther Bridges, Malin Åkerblom, Siv Beckman, Sven Påhlman

Lund University, Malmö, Sweden, Sweden

Abstract

Role of PI3K signalling pathway in modulating hypoxia response in neuroblastoma

Background

High hypoxia-inducible factor (HIF)-2α expression in neuroblastoma correlates to unfavourable outcome. HIF-2α, but not HIF-1α, was also found strongly expressed in well-vascularised areas of tumours; subsequent in vitro studies revealed HIF-2α protein stabilisation at 5% oxygen (resembling end capillary oxygen conditions) and, in contrast to the low HIF-1α activity at this oxygen level, actively transcribed genes like VEGF (Holmquist-Mengelbier L, Cancer Cell, 10:413-23, 2006). We examined the role of phosphatidylinositol 3’-kinase (PI3K)/AKT/mTOR signalling in modulating HIF-1α and HIF-2α expression and endogenous VEGF following culture of neuroblastoma cells at 1% and 5% oxygen.

Method

We investigated the effects of LY294002 (50