Phorbol esters support the proliferation of a hematopoietic cell line by upregulating 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-myristate 13-acetate, PMA) or IL-3. Analysis of immediate-early gene expression revealed that FD/PMA cells contained elevated levels of c-jun transcripts when grown in the presence of phorbol esters. Upregulation of c-jun mRNA was specific since other jun family members (namely jun-B and jun-D) displayed similar patterns of gene expression as observed 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 stability. Furthermore, elevated c-jun expression resulted in increased AP-1 binding activity in FD/PMA cells. Antisense c-jun oligonucleotides suppressed proliferation of FD/PMA cells by 80% and resulted in a significant reduction in both AP-1 binding activity and c-jun message levels. Collectively, these results demonstrate that FD/PMA cells require elevated levels of c-jun expression for PMA-responsive proliferation and indicate that tumor promoters have the ability to abrogate IL-3 dependency by elevating AP-1 activity.
Mayo
M W
MW
Department of Microbiology & Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Steelman
L S
LS
McCubrey
J A
JA
D001483:Base Sequence; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D006207:Half-Life; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D007377:Interleukin-3; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate