Inhibition of NF-κB signaling interferes with phorbol ester-induced growth arrest of keratinocytes in a TNFR1-independent manner

• Published in: Journal of receptors and signal transduction Vol. 29; no. 1; pp. 44 - 51
• Main Authors: Sur, Inderpreet, Ulvmar, Maria, Jungedal, Roger, Toftgård, Rune
• Format: Journal Article
• Language: English
• Published: Informa UK Ltd 01-02-2009; Taylor & Francis
• Subjects: carcinogenesis; Cell cycle; proliferation; signaling; tumor promoter
• ISSN: 1079-9893; 1532-4281
• DOI: 10.1080/10799890802679876

A skin-specific block in NF-κB signaling leads to hyperproliferation of the keratinocytes, inflammation, and spontaneous development of squamous cell carcinoma (SCC). Here we show that an inhibition of NF-κB signaling in keratinocytes, via the expression of the super-repressor/ degradation-resistant form of the IκBα protein (IκBαDN), interferes with the growth arrest induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). The IκBαDN cells are able to overcome the TPA-induced cell cycle block. Although SCC development as well as hyperproliferation due to IκBαDN expression in keratinocytes is known to require TNFR1 signaling, the effect of IκBαDN on phorbol ester signaling is downstream/independent of TNFR1. These data thus identify an interaction between IκBαDN and the tumor promoter TPA in the growth regulation of keratinocytes. The proposed mechanism is also likely to be significant in the process of cancer development due to NF-κB inhibition.