ANTISENSE C-JUN OVERCOMES A DIFFERENTIATION BLOCK IN A MURINE ERYTHROLEUKEMIA CELL-LINE

We have studied the expression of the c-jun gene during dimethyl-sulfo xide (DMSO) induced differentiation of Friend erythroleukemia (F-MEL) cells. No expression of c-jun was detected in a differentiation-compet ent F-MEL cell line (745A) either before or after treatment with DMSO. By contrast, c-jun expression was constitutive in a F-MEL cell line ( TFP10) resistant to DMSO-induced differentiation and increased with DM SO. We have investigated the possible role of c-jun in conferring this resistance by stably transfecting either sense or antisense c-jun con structs into both differentiation-sensitive 745A and defective TFP10 c ell lines. Inhibition of c-jun expression by antisense transcripts in the TFP10 cells restored their ability to undergo erythroid differenti ation when exposed to DMSO while expression of junB or junD antisense vectors failed to do so. In addition, c-jun overexpression in the 745A cells resulted in decreased DMSO-induced differentiation. These resul ts indicate a correlation between the level of c-jun expression and th e ability of F-MEL cells to undergo DMSO-induced differentiation and s uggest that c-jun may be an important negative regulator in this proce ss.