Regulation of Cell Growth and Cyclin D1 Expression by the Constitutively Active FRAP-p70 Pathway in Human Pancreatic Cancer Cells

The FRAP-p70 signaling pathway was found to be constitutively phosphorylated/active in MiaPaCa-2 and Panc-1 human pancreatic cancer cells and a pancreatic cancer tissue sample as judged by the retarded electrophoretic mobility of the two major FRAP downstream targets, p70 and 4E-BP1. Treatment of cells with rapamycin, a selective FRAP inhibitor, inhibited basal p70 kinase activity and induced dephosphorylation of p70 and 4E-BP1. Moreover, rapamycin inhibited DNA synthesis as well as anchorage-dependent and -independent proliferation in MiaPaCa-2 and Panc-1 cells. Finally, rapamycin strikingly inhibited cyclin D1 expression in pancreatic cancer cells. Thus, inhibitors of the constitutively active FRAP-p70 pathway may provide a novel therapeutic approach for pancreatic cancer.