Upon a brief exposure of ER silenced breast cancer cells to extracellular alkaline environment (pH 7.7-8.3), the activity of several ion pumps particularly Na+/K+ and Na+/H+ exchangers are modulated which leads to reduced phosphorylation level of three key intracellular signaling molecules; p38 MAPK, Akt, and ERK1/2, and enhanced expression profile of several adhesion molecules such as FAK, JAM-1 and 2, and integrin α 2. This evidence concerns the gene MAPK3 and breast cancer.