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Ca 2 + ‐activated K + channels in human melanoma cells are up‐regulated by hypoxia involving hypoxia‐inducible factor‐1α and the von Hippel‐Lindau protein
Author(s) -
Tajima Nobuyoshi,
Schönherr Kristina,
Niedling Susanna,
Kaatz Martin,
Kanno Hiroshi,
Schönherr Roland,
Heinemann Stefan H.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.096818
Subject(s) - hypoxia (environmental) , hypoxia inducible factors , apamin , cell culture , melanoma , charybdotoxin , biology , microbiology and biotechnology , chemistry , cancer research , endocrinology , medicine , potassium channel , gene , biochemistry , oxygen , genetics , organic chemistry
Under chronic hypoxia, tumour cells undergo adaptive changes involving hypoxia‐inducible factors (HIFs). Here we report that ion currents mediated by Ca 2 + ‐activated K + (K Ca ) channels in human melanoma IGR1 cells are increased by chronic hypoxia (3% O 2 ), as well as by hypoxia mimetics. This increase involves the HIF system as confirmed by overexpression of HIF‐1α or the von Hippel‐Lindau tumour suppressor gene. Under normoxic conditions the K Ca channels in IGR1 cells showed pharmacological characteristics of intermediate conductance K Ca subtype IK channels, whereas the subtype SK2 channels were up‐regulated under hypoxia, shown with pharmacological tools and with mRNA analysis. Hypoxia increased cell proliferation, but the K Ca channel blockers apamin and charybdotoxin slowed down cell growth, particularly under hypoxic conditions. Similar results were obtained for the cell line IGR39 and for acutely isolated cells from a biopsy of a melanoma metastasis. Thus, up‐regulation of K Ca channels may be a novel mechanism by which HIFs can contribute to the malignant phenotype of human tumour cells.