Kinase suppressor of Ras 2 is involved in regulation of cell proliferation and is up-regulated in human invasive ductal carcinomas of breast

Abstract

Aim: To study the expression of Kinase Suppressor of Ras 2 (KSR2) in human breast tumors and its effect on proliferation of breast epithelial cells. We reported previously that KSR2 was up-regulated in immortalized human breast epithelial cells. Methods: Proteomics technologies, systems biology tool for a KSR2 network analysis, immunoblotting, siRNA technology, overexpression of KSR2, cell proliferation assays and immunohistochemistry of tissue microarray of human breast tumors and normal breast tissue were used. Results: In conditionally immortalized primary epithelial cells KSR2 expression was shown to be up-regulated. The involvement of KSR2 in regulation of cell proliferation was predicted by a KSR2-centered network analysis. We observed that KSR2 down-regulation with specific siRNA inhibited cell proliferation. By immunohistochemistry of tissue microarray it was demon strated that KSR2 expression was enhanced in human invasive breast carcinomas. Conclusion: Our findings propose KSR2 as a new marker of immortalization, which has an impact on cell proliferation.