Cellular overexpression of Aquaporins slows down the natural HIF-2a degradation during prolonged hypoxia

Abstract

Overexpression of cell membrane aquaporins (AQPs) has been linked to tumor formation, particularly through angiogenesis, cell migration, and proliferation. This study investigates the effect of AQP overexpression on the stability of HIF-2α in PC12 cells under chronic hypoxia, a condition typical of growing tumors. The results show that overexpression of AQP1, AQP3, or AQP5 in PC12 cells prevents the usual downregulation of HIF-2α observed after 16 hours at 1% oxygen. This prolonged stability of HIF-2α leads to higher levels of its target genes (PHD2, PHD3, VEGF, and PGK1) and results in morphological changes and increased cell proliferation, suggesting a more tumor-like phenotype. Additionally, under normoxia, AQP-overexpressing cells show reduced expression of PHD3, indicating a complex regulatory mechanism.

Versión enviada a la editorial. Se puede consultar la versión final en https://doi.org/10.1016/j.gene.2013.03.075