Similarity in the functions of HIF-1α and HIF-2α proteins in cervical cancer cells

Abstract

Hypoxia is a common feature of many solid tumours, including cervical cancer. Aggressive tumour progression is mostly associated with hypoxia. Furthermore, hypoxic conditions in tumours are also associated with resistance to chemotherapy and radiation, and with poor prognosis. Hypoxia inducible factor (HIF)-1, composed of a constitutively expressed β-subunit (HIF-β/ARNT) and one of the three known oxygen-regulated α-subunits, HIF-1α, HIF-2α, or HIF-3α, mediates the tumour cell response to hypoxia. The distinction between the roles of HIF-1α and HIF-2α in tumorigenesis is not clearly delineated. Therefore, the aim of the present study was to investigate the effect of HIF-2α on the characteristics of a cervical cancer cell line and to compare the functions of HIF-1α and HIF-2α. The present study demonstrated that the levels of HIF-1α and HIF-2α expression increased under hypoxic exposure compared with normoxia. The major difference was the temporal expression of HIF-1α and HIF-2α, with expression of the two proteins peaking at different time-points. In addition, HIF-1α and HIF-2α had similar effects on proliferation, cell cycle and apoptosis. Suppression of expression of HIF-1α or HIF-2α inhibited proliferation, induced G1-phase arrest and promoted apoptosis in the cervical cancer cell line CaSki. However, the effects of HIF-1α and HIF-2α on invasion and cell autophagy were different. The inhibitory effect of HIF-1α on cell invasion was stronger compared with HIF-2α, while the inhibitory effect of HIF-1α on cell autophagy was weaker compared with HIF-2α. Together, these results demonstrate that HIF-1α and HIF-2α have similar effects on the characteristics of a cervical cancer cell line. The major difference that the authors observed between the effects exerted by the two proteins on the cervical cancer cell line studied is the extent of their effect on invasion and autophagy.