Regulation of VEGF, HIF-2α, and TIMP-1 in human breast cancer cells by angiotensin II and its receptor antagonist candesartan

1. Background:

The present study examined the effect of angiotensin II on the regulation of different angiogenesis associated genes in human breast cancer cells and attempted to determine whether administration of At₁R blocker candesartan could suppress the angiotensin II dependent gene regulation.

2. Methods:

Angiotensin II dependent expression of vascular endothelial growth factor (VEGF), tissue inhibitor of matrix metalloproteinases 1 (TIMP-1), and hypoxia inducible transcription factor 2α (HIF-2α) as well as administration of angiotensin II and At₁R blocker candesartan was analyzed in MDA-MB 468 human breast cancer cells using immunofluorescence and TaqMan-Real-Time PCR analysis.

3. Results:

VEGF, TIMP-1, HIF-2α and the At₁R were expressed in MDA-MB 468 human breast cancer cells. Angiotensin II significantly increased gene expression of VEGF, TIMP-1, and HIF-2α in these cells. This effect was completely inhibited by candesartan.

4. Conclusion:

It is hypothesized that angiotensin II is involved in regulation of tumor angiogenesis in breast cancer by regulation of angiogenesis associated genes via At₁R.

These findings are the first evidence for targeting tumor angiogenesis by inhibition of At₁R in human breast cancer cells and may lead to new therapeutical anticancer strategies proposing administration of candesartan.

Keywords: breast cancer cell, angiogenesis, angiotensin II, inhibition, candesartan