Zinc Induces Normoxic Accumulation Of Transcriptionally Active Hypoxia-Inducible Factor 1-Alpha In Mammary Epithelial Cells

Both zinc and the alpha-subunit of hypoxia-inducible factor (HIF-1 alpha) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1 alpha in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A mammary epithelial cell lines, the toxicity levels of zinc differ. Interestingly, both cell lines over-express HIF-1 alpha following zinc treatment. As it was evident from an up-regulation of its specific target gene CA9 that encodes carbonic anhydrase IX, the stabilized HIF-1 alpha translocated to the nucleus and was transcriptionally active. Hence, we conclude that zinc causes normoxic accumulation of transcriptionally active HIF-1 alpha by interfering with its post-translational regulation.