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Title: Does Angiotensin-(1-7) Exert its Anti-cancer Activity in Breast Tumor Cells via Inhibition of Epidermal Growth Factor Receptor Tyrosine Kinase Signaling?
Authors: بتول أكبر 
Supervisor: Prof. Saghir Akhtar
Keywords: Does Angiotensin-(1-7) Anti-cancer Breast Tumor Cells Epidermal Growth Factor Receptor Tyrosine Kinase
Issue Date: 2014
Publisher:  Kuwait university - college of graduate studies
Abstract: iv ABSTRACT Breast cancer (BC) has greatly spread in both developed and developing countries in the world with 1.38 million new cases annually. In Kuwait BC results in one in every nine deaths, and affects more than 30 percent of Kuwaiti women. Despite the availability of various therapeutic agents against BC, many are resistant-prone, therby intesifying the need for an effective treatment in targeting the aggressive Triple Negative (TN) subtype. Activation of the epidermal growth factor receptor (EGFR) family of receptor kinases plays a major role in the proliferation and cell survival of breast tumours. Angiotensin II (Ang II) peptide from the renin-angiotenisn system has been shown to stimulate BC proliferation through the Angiotensin Type 1 (AT1) receptor. In this study, the anti-proliferative effects of Angiotensin (1-7) (Ang-(1-7)) were investigated in two BC cell lines (MDA-MB-231 and MCF-7). Ang-(1-7) inhibits EGFR/ErbB2 signaling in both MDA-MB-231 and MCF-7 BC cell lines in a dose-and time-dependent manner. Cell viability assays revealed that lower doses of Ang-(1-7) inhibit MDA-MB-231 cell proliferation. Western analysis showed that Ang-(1-7) counteracts Ang II mediated stimulation of MCF-7 BC cell lines. Ang-(1-7) significantly inhibited phosphorylation of EGFR and ErbB2, as well as the downstream effectors of the MAPK pathway ERK1/2 in MDA-MB-231. Furthermore, the expression levels of both c-Src and YES were reduced in MDA-MB-231 cells treated with Ang-(1-7). Ang-(1-7) Mas Receptor antagonist Dpro-7 counteracted Ang-(1-7)- mediated inhibition of EGFR/ErbB2 signaling cascade. To the best of our knowledge, this is the first report on the mechanistic action of Ang-(1-7) in TN BC cell lines, wherein the EGFR/ErbB2/ERK1/2 derived MAPK pathway as well as downstream effectors a c-Src/YES are blocked by Ang-(1-7) via Mas receptor dependent mechanism. These results suggest that Ang-(1-7) may be beneficial in the treatment of breast tumors.
Appears in Programs:2050 Molecular Biology

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