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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hinata, K; Gervin, AM; Jennifer Zhang, Y; Khavari, PA

Published Date

  • April 3, 2003

Published In

Volume / Issue

  • 22 / 13

Start / End Page

  • 1955 - 1964

PubMed ID

  • 12673201

Pubmed Central ID

  • 12673201

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1206198

Language

  • eng

Conference Location

  • England