AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma

Abstract

Amyloid precursor protein (APP) has been implicated in squamous cell carcinoma. In this study we show that forced expression of the transcription factor activating protein 2α (AP-2α) results in significantly increased steady state levels of APP mRNA in human keratinocytes. Sequence analysis of the 5′ end of the human APP gene revealed five putative binding sites for AP-2, suggesting that APP is a direct target for transactivation by AP-2. AP-2 protein bound at least 3 of these putative promoter elements in vitro as determined by electrophoretic mobility shift assay. Chromatin immunoprecipitation (ChIP) analysis showed that these binding sites were occupied by AP-2 in cells, thus indicating the relevance to AP-2 binding in vivo. We then analyzed APP and AP-2 mRNA and protein expression in squamous cell carcinoma tumor samples. Analysis of RNA extracted from human tissue showed a significant positive correlation between AP-2α and APP mRNA expression. Immunohistochemical staining of tumor samples also demonstrated a positive correlation which was substantiated through western blot studies. Taken together, these findings demonstrate a role for the transcription factor AP-2α in the regulation of APP gene expression in human keratinocytes.