CA IX is upregulated in CoCl2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer

Int J Oncol. 2016 Jan;48(1):271-80. doi: 10.3892/ijo.2015.3253. Epub 2015 Nov 19.


Hypoxia, a common phenomenon during the development of malignant solid tumors including breast cancer, serves to propagate a cascade of molecular pathways triggered by hypoxia-inducible factor-1α (HIF-1α). Carbonic anhydrase IX (CA IX), one of the target genes of HIF-1α, has been reported to be involved in progression of malignant tumors. The objective of this study was to investigate the expression of HIF-1α and CA IX in hypoxia, involvement of CA IX in the regulation of migration and invasion/metastasis and its prognostic significance in breast cancer. We used cobalt chloride (CoCl2) as a hypoxia-mimetic agent and found that the expression of HIF-1α protein, CA IX mRNA and protein, is effectively upregulated, except for HIF-1α mRNA. Data showed that the elevated CA IX expression is closely related to in vitro cell migration and invasion, and the underlying mechanism of this process may be associated with epithelial-mesenchymal transition (EMT). The study of clinical tissue samples also demonstrated that CA IX is an independent prognostic marker that may serve as a useful clinical biomarker for predicting tumor progression and the invasion/metastasis of breast cancer. These results provide further insight into the role of CA IX in tumor progression and put forward further strong evidence as well as new consideration for CA IX target therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / biosynthesis*
  • Carbonic Anhydrases / genetics
  • Cell Hypoxia / drug effects
  • Cell Proliferation / genetics
  • Cobalt / toxicity
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • MCF-7 Cells
  • Middle Aged
  • Prognosis
  • Transcriptional Activation / drug effects


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Cobalt
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • cobaltous chloride