Interleukin-7 up-regulates cyclin D1 via activator protein-1 to promote proliferation of cell in lung cancer

Interleukin-7 is a potent regulator of lymphocyte proliferation, but it inducing growth of solid tumors is few known. We study the relationship between Interleukin-7 and the regulator of the cell cycle, cyclin D1 and the mechanism of Interleukin-7 regulating cell growth in human lung cancer. We detected expression of cyclin D1 and its impact on the prognosis of lung cancer patients. Using Western blot, reverse transcriptase-PCR, Co-Immunoprecipitation, and Chromatin Immunoprecipitation, we investigated how Interleukin-7 regulated cyclin D1 in vitro and in nude mice. We found that, in lung cancer cell lines and in nude mice, Interleukin-7/Interleukin-7 receptor increased the expression of cyclin D1 and phosphorylation of c-Fos/c-Jun, induce c-Fos and c-Jun heterodimer formation, and enhanced c-Fos/c-Jun DNA-binding activity to regulate cyclin D1. In addition, lymph node metastasis, tumor stage, and cyclin D1 were the strongest predictors of survival in 100 human non-small cell lung cancer specimens analyzed. Taken together, our results provided evidence that Interleukin-7/Interleukin-7 receptor induced cyclin D1 up-regulation via c-Fos/c-Jun pathway to promote proliferation of cells in lung cancer.