HIF-1a induces downregulated expression of Aurora A in breast cancer cell lines

Background: Aurora A (AURKA) is an oncogenic serine/treonine kinase that play a critical role during mitosis, governing the correct distribution of genetic material to the daughter cells. AURKA is overexpressed in many types of human tumors including breast cancer and its deregulated expression, inducing alteration of mitotic spindle, chromosomal segregation and aneuploidy can lead to malignant transformation of cells. Aims: Since hypoxia is a typical tumoral condition which influences the expression of various proteins involved in proliferation and cell cycle progression, aim of our study was to obtain new insights into AURKA regulation in breast cancer cell lines cultured under normoxic and hypoxic conditions. Materials and Methods: Microarray analysis, using Affymetrix platform, was performed in MCF7, MDA-MB-231 and SKBr3 cells, in order to compare the differential gene expression profile in response to hypoxia. This analysis showed AURKA downregulation in all breast cancer cell lines analyzed and the reduction of both mRNA levels and related protein were confirmed by Real-Time RT-PCR and Western Blotting. The HIF-α involvement in transcriptional control of AURKA were assess by ChiP assay and siRNA against HIF-1α was used to inhibit the HIF-1α induction during hypoxia. Results: Our data showed that hypoxic condition induces a reduction of AURKA expression suggesting a possible direct involvement of HIF-1α in this downregulation. Conclusions: These results suggest a new mechanism of AURKA regulation that might be able to suppress the proliferation, lead to the apoptosis of breast cancer cell lines and play a key role in the realization of new possible therapeutic approaches.