The serine/threonine kinase p70s6k was found to be constitutively phosphorylated in H 69, H 345, and H 510 small cell lung cancer cells as judged by the retarded electrophoretic mobility of both isoforms of this kinase. Pretreatment of H 69, H 345, and H 510 cells with the potent immunosuppressant rapamycin led to p70s6k dephosphorylation in a concentration-dependent manner; half-maximum and maximum effects were achieved at 0.3 and 3 nm rapamycin, respectively. Rapamycin inhibited growth of H 69, H 345, and H 510 cells in liquid culture at similar concentrations to those required for inducing dephosphorylation of p70s6k. Furthermore, rapamycin markedly reduced the basal colony forming ability of H 69, H 345, and H 510 cells in semisolid media. Thus, constitutively phosphorylated/active p70s6k plays an important role in promoting the growth of small cell lung cancer cells. Furthermore, the rapamycin-sensitive p70s6k pathway may provide a novel target for therapeutic intervention in small cell lung cancer.

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