Temporal profiling of a breast cancer cell line MCF-7 in response to reoxygenation
Journal
Proceedings of the American Association for Cancer Research Annual Meeting
Journal Volume
51
Pages
106
Date Issued
2010
Author(s)
Abstract
Abstract Oxygen fluctuation resulting from hyper-proliferation of tumor cells, abnormal metabolism and disorganized tumor neovasculature characterizes the microenvironment of many cancers, which influences tumor development and angiogenesis. Furthermore, this condition increases chemo-resistance and radio-resistance of tumor cells, and also associates with increased invasion and metastatic potential accompanied with a poor prognosis. Hypoxia/ reoxygenation induce oxidative stress, which leads to DNA damage and genomic instability. It is known that multiple cellular responses were activated in order to survive under this microenvironment, but little is known about the dynamic response upon reoxygenation. To investigate the dynamic response of signalling pathways in tumor adaptation, a breast cancer cell line MCF-7 was cultured under 0.5% oxygen condition 24 hours followed by reoxygenation, and was harvested at various time points during reoxygenation. Genome-wide microarray results revealed that 274 genes were differentially expressed during reoxygenation; 47.4% of them were up-regulated and 52.3% down-regulated. Furthermore, pathway analysis, including canonical pathway and gene network, were performed using Ingenuity Pathway Analysis. Selected genes of interest were validated by quantitative real-time PCR, such as hexokinase 2 (HK2) and cyclin D3 (CCND3). Survival analysis using clonogenic assay showed little effect of reoxygenation on MCF-7 cells, but proliferation was inhibited upon reoxygenation. Our result showed dynamic changes of MCF-7 gene expression and molecular pathways unpon reoxygenation, which shed some light on understanding of tumor adaptation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 441.
SDGs
Type
journal article