Abstract 1076: Activation of H-Ras and Rac1 correlates with epidermal growth factor-induced breast cell invasion

Abstract

Abstract There are considerable experimental evidences that hyperactive Ras proteins promote breast cancer growth and development including invasiveness despite of low frequency of mutated forms of Ras in breast cancer. We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells. Epidermal growth factor (EGF) plays important roles in aberrant growth and metastasis formation of many tumor types including breast cancer. Here, we investigated the involvement of H-Ras in the EGF-induced invasive ability of four different breast cancer cell lines. Upon EGF stimulation, H-Ras activation was increased in the invasive breast cancer cells, MDA-MB-231 and Hs578T cells, but not in non-invasive breast cancer cells, MDA-MB-453 and T47D cells. Using small interfering RNA (siRNA) targeting H-Ras, we showed a crucial role of H-Ras in invasive phenotype induced by EGF in MDA-MB-231 and Hs578T cells. Moreover, knockdown of Rac1significantly inhibited the EGF-induced invasiveness in these cells. Taken together, our data demonstrate that the activation of H-Ras and its downstream molecule Rac1 correlates with breast cancer cell invasion induced by EGF, providing useful information on the regulation of malignant progression in mammary carcinoma. [This work was supported by the Korea government (Nos.ROA-2008-000-20070-0)] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1076. doi:10.1158/1538-7445.AM2011-1076