Abstract
Angiotensin II (Ang II) is a bioactive peptide of the renin–angiotensin system, acting not only as a vasoconstrictor but also as a growth promoter via angiotensin II type 1 receptor (AT1R) in some cancer. In this study, we examined the mechanisms by which Ang II affected the cell proliferation in AT1R‐positive MCF‐7 human breast cancer cells. Ang II stimulated the growth of breast cancer cells in a dose‐ and time‐dependent manner. The maximal proliferation effect on MCF‐7 cells was obtained with 10^−4^ M Ang II at 24 h. Losartan (10^−5^ M, an AT1R antagonist) significantly decreased the level of Ang‐II‐induced proliferative effects, whereas PD123319 (10^−5^ M, an AT2R antagonist) had no effects. Moreover, Ang II could significantly accelerate S‐phase progression, which was inhibited by losartan (10^−5^ M) or LY294002 (50 µM, a PI3‐kinase inhibitor). In addition, Ang II caused rapid activation of p‐Akt in a dose‐ and time‐dependent manner. 10^−4^ M Ang II induced a significant increase of p‐Akt in 15 min. The peak level of p‐Akt could be persisted for at least 6 h. Among the signaling molecules downstream of Akt, we revealed that Ang II also significantly upregulated CyclinD1, GSK3β, and downregulated p27. Pretreatment with losartan (10^−5^ M) or LY294002 (50 µM) could significantly suppress these effects of Ang II. These findings suggest that Ang II plays a role in the growth of AT1R‐positive breast cancer cells through PI3‐kinase/Akt pathway activation. Therefore, targeting Ang II/AT1R signaling could be a novel therapeutic for breast cancer. J. Cell. Physiol. 225: 168–173, 2010. © 2010 Wiley‐Liss, Inc.