Zinc induces normoxic accumulation of transcriptionally active hypoxia-inducible factor 1-alpha in mammary epithelial cells

Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A...

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Bibliographic Details
Main Authors: Lee, S. Y., Mustafa, S., Ching, Y. W., Shafee, Norazizah
Format: Article
Language:English
Published: Federation of European Biochemical Societies 2017
Online Access:http://psasir.upm.edu.my/id/eprint/46918/
http://psasir.upm.edu.my/id/eprint/46918/1/Zinc%20induces%20normoxic%20accumulation%20of%20transcriptionally%20active%20hypoxia-inducible%20factor%201-alpha%20in%20mammary%20epithelial%20cells.pdf
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Summary:Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α 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 overexpress HIF-1α 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-1α translocated to the nucleus and was transcriptionally active. Hence, we conclude that zinc causes normoxic accumulation of transcriptionally active HIF-1α by interfering with its post-translational regulation.