There is considerable experimental evidence that hyperactive Ras proteins 
promote breast cancer growth and development including invasiveness, despite the 
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 an important role in aberrant growth and metastasis formation of 
many tumor types including breast cancer. The present study aims to investigate 
the correlation between EGF-induced invasiveness and Ras activation in four 
widely used breast cancer cell lines. Upon EGF stimulation, invasive abilities 
and H-Ras activation were significantly increased in Hs578T and MDA-MB-231 cell 
lines, but not in MDA-MB-453 and T47D cell lines. Using small interfering RNA 
(siRNA) to target H-Ras, we showed a crucial role of H-Ras in the invasive 
phenotype induced by EGF in Hs578T and MDA-MB-231 cells. Moreover, 
siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in 
these cells. Taken together, this study characterized human breast cancer cell 
lines with regard to the relationship between H-Ras activation and the invasive 
phenotype induced by EGF. Our data demonstrate that the activation of H-Ras and 
the downstream molecule Rac1 correlates with EGF-induced breast cancer cell 
invasion, providing important information on the regulation of malignant 
progression in mammary carcinoma cells.