AP-2 gene expression and modulation by retinoic acid during keratinocyte differentiation

The transcription factor AP-2 has been suggested to participate in keratinocyte gene regulation, but its precise role in the processes of keratinocyte proliferation and differentiation is largely unknown. We here report on an increase of AP-2 transcripts in proliferating HaCaT keratinocytes preceding the expression and upregulation of the differentiation-related genes keratin 4 (K4) and Ah-receptor (AhR), but a decrease of AP-2 transcript levels during the process of keratinocyte differentiation. Continuous treatment of the keratinocyte cell cultures with retinoic acid (RA) resulted in a premature downregulation of AP-2 mRNA levels, and the transcripts of K4 and AhR remained at basal levels. Furthermore, addition of RA to already differentiated cells failed to exert any effect on K4- and AhR-mRNA levels. The data suggest a role for AP-2 as an intermediate factor in the pathway of RA action in keratinocyte differentiation, explaining both the downregulation of K4 and AhR transcript levels in proliferative keratinocytes and the loss of RA effects in already differentiated cells. It appears thus that AP-2 plays a pivotal role at the onset of differentiation in still proliferating keratinocytes.