Role and mechanism of hypoxia-inducible factor-1 in cell growth and apoptosis of breast cancer cell line MDA-MB-231.

The role of hypoxia-inducible factor-1 (HIF-1) in tumor development and progression is well-established but its effect on tumor growth remains controversial. The present study investigated the effect of HIF-1 on tumor growth using the estrogen receptor-negative breast cancer cell line, MDA-MB-231. Using Western blotting, we detected a higher level of HIF-1α protein in MDA-MB-231 cells than in any other breast cancer cell lines analyzed, and this was accompanied by a more rapid growth pattern. Interruption of HIF-1α expression using small interference RNA (siRNA) significantly suppressed cell growth and increased apoptosis, but the cell cycle was not affected. Activated fragments with increased caspase 3 activity and a mobility shift of B cell lymphoma (Bcl-2) were also detected in cells treated with HIF-1α siRNA. HIF-1 allows breast cancer cells to grow under long-term serum deprivation by inactivation of the caspase cascade and thus inhibition of apoptosis. Blocking HIF-1α protein resulted in loss of Bcl-2 function, which may contribute to the activation of the caspase cascade.