Saito Y, Ogawa K
Department of Pathology, Asahikawa Medical College, Japan.
Oncogene. 1995 Sep 21;11(6):1013-8.
p53 and c-myc are both known to be involved in apoptotic cell death as well as positive or negative regulation of cell proliferation, but it is not well established whether their functions are mechanistically correlated. We found that FAA-HTC1 cells, a rat hepatocellular carcinoma cell line, expressed c-myc independently of cell cycle and no detectable p53. To investigate possible co-operation between p53 and c-myc, the dexamethasone (Dex)-inducible wild type rat p53 was stably transfected into this cell line and c-myc expression was suppressed by treatment with c-myc antisense oligonucleotide (AS). p53 expression in the p53-introduced derivative resulted in apoptotic cell death, but it did not inhibit proliferative growth of the viable cells. On the other hand, when c-myc was suppressed in the p53-expressing cells, both apoptosis and cell growth were inhibited. These results indicate that p53 can act in the same cells either as a growth-inhibitor or apoptosis-inducer depending on the status of c-myc expression.
已知p53和c-myc都参与凋亡性细胞死亡以及细胞增殖的正负调节，但它们的功能在机制上是否相关尚不清楚。我们发现，FAA-HTC1细胞系（一种大鼠肝癌细胞系）独立于细胞周期表达c-myc且未检测到p53。为了研究p53和c-myc之间可能的协同作用，将地塞米松（Dex）诱导型野生型大鼠p53稳定转染到该细胞系中，并用c-myc反义寡核苷酸（AS）处理抑制c-myc表达。在引入p53的衍生物中p53表达导致凋亡性细胞死亡，但它并未抑制存活细胞的增殖生长。另一方面，当在表达p53的细胞中抑制c-myc时，凋亡和细胞生长均受到抑制。这些结果表明，根据c-myc表达状态，p53在同一细胞中既可以作为生长抑制剂，也可以作为凋亡诱导剂发挥作用。
