Transcriptome analysis of breast cancer cell line exposed to hypoxia-mimetic chemical CoCl2 or hypoxic microenvironment

Hypoxia is a common feature of solid tumors, including breast cancer, and is related to aggressiveness and poor prognosis. The hypoxia-inducible factor 1, HIF-1, is the central transcriptional factor of response to hypoxia. Hypoxia-inducing methods, as low oxygen level and chemical compound cobalt(II) chloride (CoCl2) block HIF-1α degradation, that moves to the cell's nucleus and promotes the expression of its target genes. However, the effects on gene expression profiles driven by each hypoxia inducer are little known in breast cancer. This work aims to compare differential expression genes and pathways induced by CoCl2 or hypoxia chamber in MDA-MB-231 breast cancer cell line. Transcriptomes were conducted on Human Chip 1.0 exon from CoCl2-treated cells or hypoxic conditions. Differential gene expression profiles were clustered using DAVID and FunRich, to determine cellular components and signaling pathways. Both CoCl2 treatment and hypoxia chamber upregulated genes involved in response to hypoxia and downregulated genes clustered in FoxO signaling pathway, Wnt signaling pathway, Fanconi anemia pathway and non-homologous end-joining. Several canonical signaling pathways and energy metabolism were altered only after hypoxia chamber. CoCl2 altered glutathione, amino acid metabolism, endocytosis and PI3K-Akt genes. We observed greater amount of genes, cellular components and pathways altered after hypoxia chamber than CoCl2 treatment. The findings suggest that despite the similarities, CoCl2 treatment and hypoxia chamber also promote exclusive effects of each method. Then, depending of objective, they cannot be interchangeable, considering mainly gene expression studies that have as model MDA-MB-231 breast cancer cell line.