title: [Zinc induces normoxic accumulation of transcriptionally active hypoxia-inducible factor 1-alpha in mammary epithelial cells].
abstract: 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.
authors.affiliation: Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 UPM Serdang, Malaysia.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 UPM Serdang, Malaysia.
authors.forename: S
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 UPM Serdang, Malaysia.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Ching
authors.affiliation: Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 UPM Serdang, Malaysia.|nshafee@upm.edu.my.
authors.forename: N
authors.initials: N
authors.lastname: Shafee
mesh_terms: D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002467:Cell Nucleus; D004847:Epithelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D015032:Zinc
keywords: hypoxia-inducible factor; mammary epithelial cells; zinc