Hinata Kaede, Gervin Adam M, Jennifer Zhang Y, Khavari Paul A
Program in Epithelial Biology, Stanford University School of Medicine, CA 94305, USA.
Oncogene. 2003 Apr 3;22(13):1955-64. doi: 10.1038/sj.onc.1206198.
NF-kappa B regulates normal and pathological processes, including neoplasia, in a tissue-context-dependent manner. In skin, NF-kappa B is implicated in epidermal homeostasis as well as in the pathogenesis of squamous cell carcinoma; however, its function in the underlying mesenchymal dermis has been unclear. To gain insight into NF-kappa B roles in these two adjacent cutaneous tissue compartments, NF-kappa B effects on expression of 12 435 genes were determined in epidermal keratinocytes and dermal fibroblasts. Although NF-kappa B induced proinflammatory and antiapoptotic genes in both settings, it exhibited divergent effects on growth regulatory genes. In keratinocytes, but not in fibroblasts, NF-kappa B induced p21(CIP1), which was sufficient to inhibit growth of both cell types. Levels of growth inhibitory factor (GIF), in contrast, were increased by NF-kappa B in both settings but inhibited growth only in keratinocytes. These findings indicate that transcription factors such as NF-kappa B can program tissue-selective effects via both differential target gene induction as well as by inducing common targets that exert differing effects depending on cellular lineage.
核因子κB（NF-κB）以组织背景依赖的方式调节包括肿瘤形成在内的正常和病理过程。在皮肤中，NF-κB参与表皮稳态以及鳞状细胞癌的发病机制；然而，其在下方间充质真皮中的功能尚不清楚。为了深入了解NF-κB在这两个相邻皮肤组织隔室中的作用，研究人员在表皮角质形成细胞和真皮成纤维细胞中测定了NF-κB对12435个基因表达的影响。尽管NF-κB在两种情况下均诱导促炎和抗凋亡基因，但它对生长调节基因表现出不同的影响。在角质形成细胞中，而非成纤维细胞中，NF-κB诱导p21（CIP1），这足以抑制两种细胞类型的生长。相比之下，生长抑制因子（GIF）的水平在两种情况下均被NF-κB升高，但仅在角质形成细胞中抑制生长。这些发现表明，诸如NF-κB之类的转录因子可通过差异靶基因诱导以及诱导根据细胞谱系发挥不同作用的共同靶标来编程组织选择性效应。
