P5-07-06: Effect of Angiotensin-(1-7) and Angiotensin II on T47D Breast Cancer Cells in the Proliferation and cAMP Production.

Abstract

Abstract Angiotensin-(1-7) [Ang(1-7)] is a peptide hormone that produces opposite responses to those of the well-characterized peptide angiotensin II (Ang II). The main actions of Ang(1-7) and AII occur, respectively, via MAS and Angiotensin type 1 receptor (AT1R), respectively. Ang (1-7) has blood pressure and proliferative effects contrary to those of AngII, exhibits significant antiangiogenic activity and may be a novel therapeutic agent for lung cancer treatment targeting a specific AT(1-7) receptor (Soto-Pantoja et al., 2009). Here, our aim was to evaluate T47D breast cancer cell proliferation and cAMP production after treatment with Ang (1-7) and AngII.By means of the cyclic AMP (cAMP) competitive enzymeimmunoassay system we measured cAMP content of T47D cells. Cell proliferation was measured using incorporation of BrdU after Ang (1-7) and AII stimulation. Intracellular cAMP increasing drugs like Forskolin (FK) and isobutylmethylxanthine (IBMX) were also used to stimulate T47D cells.AII inhibited cAMP production (−39%) and A-(1-7) increased its formation (48%). Pattern of cAMP production was not altered when cells were previously incubated with FK. Results were inverted after IBMX incubation. In proliferation, opposite responses were observed for Ang II and Ang (1-7), that is, increasing (7.6 times) and decreasing (7.5 times) proliferation rates respectively. Also both peptides decreased proliferation when cells were stimulated by FK. Exactly the opposite happened after IBMX stimulation, both peptides increased proliferation. These results suggest that Ang (1-7) inhibits growth of T47D cells probably through inhibition of the via RAS/RAF/MAP quinase, what corroboraties previous findings. On the other hand, AngII can induce cell proliferation by an alternative via (CREB/growth factor). Therefore, Ang (1-7) seems to be not only a promising target to develop novel lung cancer therapeutic drugs, but it also might help to prevent the molecular changes that lead the normal breast epithelial cells to cancer initiation. Financial Support: FAPESP. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-06.