Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype

作者: M Barathova , M Takacova , T Holotnakova , A Gibadulinova , A Ohradanova

DOI: 10.1038/SJ.BJC.6604111

关键词: RNA splicingExonMolecular biologyMessenger RNABiologyAlternative splicingEnzymeCarbonic anhydraseCarbonic anhydrase inhibitorTransfection

摘要: CA IX is a hypoxia-induced, cancer-associated carbonic anhydrase isoform with functional involvement in pH control and cell adhesion. Here we describe an alternative splicing variant of the CA9 mRNA, which does not contain exons 8–9 expressed tumour cells independently hypoxia. It also detectable normal tissues absence full-length transcript can therefore produce false-positive data prognostic studies based on detection hypoxia- cancer-related expression. The encodes truncated protein lacking C-terminal part catalytic domain. shows diminished activity intracellular or secreted. When overexpressed, it reduces capacity to acidify extracellular hypoxic bind inhibitor. HeLa transfected cDNA generate spheroids that do form compact cores, suggesting they fail adapt stress. Our indicate functionally interfere IX. This might be relevant particularly under conditions mild hypoxia, when suffer from severe acidosis need excessive control.

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