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[Cancer Research 59, 3581-3587, August 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 3581-3587, August 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Regulation of Cell Growth and Cyclin D1 Expression by the Constitutively Active FRAP-p70s6K Pathway in Human Pancreatic Cancer Cells1

Martin Grewe, Frank Gansauge, Roland M. Schmid, Guido Adler and Thomas Seufferlein2

Departments of Internal Medicine I [M. G., R. M. S., G. A., T. S.] and Surgery [F. G.], University of Ulm, D-89081, Ulm, Germany

The FRAP-p70s6K 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, p70s6K and 4E-BP1. Treatment of cells with rapamycin, a selective FRAP inhibitor, inhibited basal p70s6K kinase activity and induced dephosphorylation of p70s6K 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-p70s6K pathway may provide a novel therapeutic approach for pancreatic cancer.




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