CYTOKINE TRIGGERED MOLECULAR PATHWAYS THAT CONTROL CELL-CYCLE ARREST

Recent progress has been made concerning the understanding of the molecular pathways that mediate the growth suppressive effects of inhibitory cytokines. Interferons, interleukin-6 and transforming growth factor-beta were investigated in these studies. Cell lines that display growth sensitivity to all three cytokines and growth resistant derivates provided a suitable genetic background to determine whether common or unique post-receptor elements mediate the effects of each cytokine. Three nuclear genes, c-myc, RB, and cyclin A were found to be common key downstream targets along the cytokine induced growth suppressive pathways. Genetic and pharmacological manipulations proved that these molecular responses fall into few complementary pathways that function in parallel to achieve the cytokine mediated G0/G1 arrest. New strategies, such as knock out anti-sense gene cloning were developed and they currently provide powerful tools for the isolation of genes along the signaling pathways of growth arrest.