ΔNp63α expression is regulated by the phosphoinositide 3-kinase pathway

p63 is a homologue of p53 that functions to maintain progenitor cell populations in stratified epithelia. DeltaNp63alpha is overexpressed in epithelial cancers and has been shown to have oncogenic properties. We have previously reported that inhibition of epidermal growth factor receptor signaling results in a decrease in DeltaNp63alpha expression. Here, we demonstrate DeltaNp63alpha is a target of the phosphoinositide-3-kinase (PI3K) pathway downstream of the epidermal growth factor receptor. Treatment of keratinocytes with epidermal growth factor results in an increase in DeltaNp63alpha expression at the mRNA level, which is abrogated by inhibition of PI3K but not mitogen-activated protein kinase signaling. Small interfering RNA-mediated knockdown of the p110beta catalytic subunit of PI3K results in a decrease in DeltaNp63alpha protein levels in keratinocytes. The results presented herein suggest that regulation of DeltaNp63alpha expression by the PI3K pathway plays a critical role in the survival and proliferative capacity of squamous epithelia.