PHORBOL ESTERS SUPPORT THE PROLIFERATION OF A HEMATOPOIETIC-CELL LINEBY UP-REGULATING C-JUN EXPRESSION

FD/PMA, a derivative of the interleukin-3 (IL-3) dependent FDC-P1 cell line, proliferates in response to either phorbol esters (phorbol 12-m yristate 13-acetate, PMA) or IL-3. Analysis of immediate-early gene ex pression revealed that FD/PMA cells contained elevated levels of c-jun transcripts when grown in the presence of phorbol esters. Upregulatio n of c-jun mRNA was specific since other jun family members (namely ju n-B and jun-D) displayed similar patterns of gene expression as observ ed in the parental cell line. The accumulation of c-jun RNA was due to increased c-jun transcription and not the result of altered message s tability, Furthermore, elevated c-jun expression resulted in increased AP-1 binding activity in FD/PMA cells, Antisense c-jun oligonucleotid es suppressed proliferation of FD/PMA cells by 80% and resulted in a s ignificant reduction in both AP-1 binding activity and c-jun message l evels. Collectively, these results demonstrate that FD/PMA cells requi re elevated levels of c-jun expression for PMA-responsive proliferatio n and indicate that tumor promoters have the ability to abrogate IL-3 dependency by elevating AP-1 activity.