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.