Divergent gene regulation and growth effects by NF-kappa B in epithelial and mesenchymal cells of human skin.
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.
Duke Scholars
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Related Subject Headings
- Transcriptional Activation
- Transcription, Genetic
- Skin
- Recombinant Fusion Proteins
- Organ Specificity
- Oncology & Carcinogenesis
- Nerve Tissue Proteins
- NF-kappa B
- NF-KappaB Inhibitor alpha
- Metallothionein 3
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcriptional Activation
- Transcription, Genetic
- Skin
- Recombinant Fusion Proteins
- Organ Specificity
- Oncology & Carcinogenesis
- Nerve Tissue Proteins
- NF-kappa B
- NF-KappaB Inhibitor alpha
- Metallothionein 3