Hypoxia-induced alterations of G2 checkpoint regulators

Molecular Oncology
Grete HasvoldRandi G Syljuåsen

Abstract

Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, genome stability is also surveilled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can influence the DNA damage-induced cell cycle checkpoints. Here, we show that hypoxia (24 h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, the levels of several G2 checkpoint regulators, in particular Cyclin B, were reduced in G2 phase cells after hypoxic exposure, as shown by flow cytometric barcoding analysis of individual cells. These effects were accompanied by decreased phosphorylation of a Cyclin dependent kinase (CDK) target in G2 phase cells after hypoxia, suggesting decreased CDK activity. Furthermore, cells pre-exposed to hypoxia showed increased G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (∼0.03% O2 20 h and 0.2% O2 72 h). These results demonstrate that the DNA damage-induced G2 checkpo...Continue Reading

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Citations

Apr 4, 2017·Biochimica Et Biophysica Acta. General Subjects·Jiří ŘehulkaViswanath Das
Apr 5, 2019·Cell Cycle·Sissel HaugeRandi G Syljuåsen
Aug 31, 2020·Cell Death Discovery·Katheryn Begg, Mahvash Tavassoli
Nov 30, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Fei FeiShiwu Zhang
Sep 4, 2020·Medicines·Angela Dalia RicciGiovanni Brandi
Feb 11, 2021·Cell Death Discovery·Katheryn Begg, Mahvash Tavassoli
Apr 29, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jian GaoChunyang Kang
Nov 3, 2021·International Journal of Radiation Biology·Eui Jung MoonMonica M Olcina

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