BUTYRATE-INDUCED REVERSAL OF DEXAMETHASONE RESISTANCE IN AUTONOMOUS RAT NB2 LYMPHOMA-CELLS

The parental rat Nb2 lymphoma is a prolactin (PRL)-dependent T cell li ne, Exposure of a PRL-independent subline, Nb2-SFJCD1, to sodium butyr ate (NaBT) causes transient reversal of their growth factor-independen t proliferation in association with constitutive expression of protoon cogenes pim-1 and c-myc, in the present study, we investigated the eff ect of NaBT treatment on the sensitivity oi Nb2-SFJCD1 cells to dexame thasone (DEX)-induced apoptosis, Pretreatment with NaBT (2 mM, 72 h) p artially reversed resistance to apoptosis in Nb2-SFJCD1 cells exposed to DEX (100 nM) for 12 h, assessed by flow cytometric analyses of DNA fragmentation. However, the cytolytic effect of DEX was abrogated by P RL in a time- and concentration-dependent manner. Evaluation of apopto sis-associated gene expression in NaBT-pretreated cultures incubated w ith DEX or DEX+PRL indicated that the apoptosis resistance did not ste m from altered bcl-2 or bax expression, However, there was a strong co rrelation between the resistance to DEX-activated apoptosis and their enhanced expression of pim-1 mRNA and protein. The results show that i t is possible to reverse DEX-induced apoptosis of Nb2 pre-T cells and suggest the pim-1 gene product has an important role as a suppressor o f this process, perhaps functioning as a mediator of PRL action.