Protein kinase C‐δ regulates the stability of hypoxia‐inducible factor‐1α under hypoxia

Hypoxia is a state of deficiency of available oxygen in the blood and tissues, and it occurs during several pathophysiological processes, including tumorigenesis. Under hypoxia, hypoxia‐inducible factor‐1 (HIF‐1) plays an essential role in cellular oxygen homeostasis. In the present article protein kinase C‐δ (PKC‐δ) is activated by hypoxia, increases the protein stability and transcriptional activity of HIF‐1α in human cervical adenocarcinoma cells. Moreover, the knockdown of PKC‐δ inhibited vascular endothelial growth factor expression and angiogenic activity under hypoxia. These effects were completely reversed by PKC‐δ overexpression following the knockdown of PKC‐δ. Collectively, these findings demonstrate the role of PKC‐δ as a new regulator of hypoxia‐induced angiogenesis. (Cancer Sci 2007; 98: 1476–1481)