Blatti S P, Scott R E
Department of Pathology, University of Tennessee Medical School, Memphis 38163.
Cell Growth Differ. 1992 Jul;3(7):429-34.
A variety of agents can induce predifferentiation growth arrest (PGA) in human keratinocytes; these include transforming growth factor beta 1 (TGF-beta 1) and razoxane. We evaluated the ability of these and other agents to induce the expression of a variety of transcription factor genes including c-fos, c-myc, junB, and c-jun. The results show that both TGF-beta 1 and razoxane induce maximal c-jun mRNA expression 4 days after initiation of treatment concurrent with the development of PGA. In contrast, no detectable induction of c-fos, c-myc, or junB was observed. Keratinocytes maintained in the presence of TGF-beta 1 for an additional 3 days continued to show high levels of c-jun mRNA, indicating stable induction. Razoxane treatment also induces PGA and high c-jun mRNA levels for 4 days, but thereafter a decay of c-jun expression occurs. Run-off transcription experiments comparing rapidly growing cells with cells treated with TGF-beta 1 for 4 days demonstrated a significant increase in transcriptional activity of the c-jun gene. This result indicates that the increase in c-jun gene expression is due in part to a change in transcriptional regulation of c-jun. The stable induction of c-jun mRNA in keratinocytes at the PGA state is unique because the induction of this gene is usually transient. The finding that c-fos is not coinduced suggests that c-Jun homodimers or other AP-1 heterodimers may be formed at the PGA state to facilitate the stable induction of c-jun mRNA. This experimental system should therefore serve as a model system to study the molecular mechanisms for the stable control of c-jun gene expression and the control of AP-1-dependent gene expression during the process of keratinocyte differentiation.
多种因子可诱导人角质形成细胞发生预分化生长停滞（PGA）；这些因子包括转化生长因子β1（TGF-β1）和雷佐生。我们评估了这些因子及其他因子诱导多种转录因子基因（包括c-fos、c-myc、junB和c-jun）表达的能力。结果显示，TGF-β1和雷佐生在治疗开始4天后均诱导c-jun mRNA表达达到最大值，同时伴有PGA的出现。相比之下，未观察到c-fos、c-myc或junB有可检测到的诱导。在TGF-β1存在下再培养3天的角质形成细胞继续显示高水平的c-jun mRNA，表明诱导稳定。雷佐生处理也诱导PGA和高水平的c-jun mRNA达4天，但此后c-jun表达出现衰减。将快速生长的细胞与用TGF-β1处理4天的细胞进行的连续转录实验表明，c-jun基因的转录活性显著增加。这一结果表明，c-jun基因表达的增加部分归因于c-jun转录调控的变化。在PGA状态下角质形成细胞中c-jun mRNA的稳定诱导是独特的，因为该基因的诱导通常是短暂的。c-fos未被共同诱导这一发现表明，在PGA状态下可能形成c-Jun同二聚体或其他AP-1异二聚体，以促进c-jun mRNA的稳定诱导。因此，该实验系统应作为一个模型系统，用于研究角质形成细胞分化过程中c-jun基因表达稳定调控的分子机制以及AP-1依赖性基因表达的调控。
