Divergent gene regulation and growth effects by NF-κB in epithelial and mesenchymal cells of human skin

• Published in: Oncogene Vol. 22; no. 13; pp. 1955 - 1964
• Main Authors: HINATA, Kaede, GERVIN, Adam M, ZHANG, Y. Jennifer, KHAVARI, Paul A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 03.04.2003; Nature Publishing Group
• Subjects: Apoptosis - genetics; Biological and medical sciences; Cell Division - drug effects; Cell Lineage; Classical genetics, quantitative genetics, hybrids; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - biosynthesis; Cyclins - genetics; Dermis; Divergence; Epithelial Cells - metabolism; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation; Gene regulation; Genes; Genetics of eukaryotes. Biological and molecular evolution; Homeostasis; Human; Humans; I-kappa B Proteins - genetics; I-kappa B Proteins - physiology; Inflammation; Inflammation - genetics; Keratinocytes; Keratinocytes - cytology; Keratinocytes - metabolism; Mesenchyme; Mesoderm - cytology; Mesoderm - metabolism; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; NF-kappa B - genetics; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; NF-κB protein; Organ Specificity; Recombinant Fusion Proteins - physiology; Skin - cytology; Skin - metabolism; Squamous cell carcinoma; Transcription factors; Transcription, Genetic; Transcriptional Activation; Human; NF-κB; Gene; Growth; GIF; p21C1P; Epithelial cell; Skin; gene expression profiling
• ISSN: 0950-9232; 1476-5594
• 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.