Mayo M W, Steelman L S, McCubrey J A
Department of Microbiology & Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Oncogene. 1994 Jul;9(7):1999-2008.
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.
FD/PMA是白细胞介素-3（IL-3）依赖的FDC-P1细胞系的衍生物，对佛波酯（佛波醇12-肉豆蔻酸酯13-乙酸酯，PMA）或IL-3有增殖反应。对早期即刻基因表达的分析表明，当在佛波酯存在的情况下生长时，FD/PMA细胞中c-jun转录本水平升高。c-jun mRNA的上调是特异性的，因为其他jun家族成员（即jun-B和jun-D）表现出与亲代细胞系中观察到的相似的基因表达模式。c-jun RNA的积累是由于c-jun转录增加，而不是信息稳定性改变的结果。此外，c-jun表达的升高导致FD/PMA细胞中AP-1结合活性增加。反义c-jun寡核苷酸将FD/PMA细胞的增殖抑制了80%，并导致AP-1结合活性和c-jun信息水平显著降低。总的来说，这些结果表明，FD/PMA细胞对PMA反应性增殖需要升高的c-jun表达水平，并表明肿瘤启动子有能力通过提高AP-1活性来消除对IL-3的依赖性。
