The AP-2α Transcription Factor Regulates Tumor Cell Migration and Apoptosis Francesca Orso, Michela Fassetta, Elisa Penna, Alessandra Solero, Katia De Filippo, Piero Sismondi, Michele De Bortoli and Daniela Taverna Institute for Cancer Research and Treatment (IRCC), Dept. Onc. Sci., University of Torino, Str. Prov. 142 – Km 3.95, 10060 Candiolo (To), Italy. daniela.taverna@unito.it Abstract. AP-2 proteins are a family of developmentally-regulated transcription factors. They are encoded by five different genes (a, b, g , d and e) but they share a common structure. AP-2 play relevant roles in growth, differentiation and adhesion by controlling the transcription of specific genes. Many evidences show that the AP-2 genes are involved in tumorigenesis and for instance they act as tumour suppressors in melanomas and mammary carcinomas. Here we investigated the function of the AP-2α protein in cancer formation and progression focusing on apoptosis and migration. We introduced AP-2α-specific siRNA (as oligos or in retroviruses) in HeLa or MCF-7 human tumor cells and obtained a pronounced down-modulation of AP-2α mRNA and protein levels. In these cells we observed a significant reduction of chemotherapy-induced apoptosis, migration and motility and an increase in adhesion suggesting a major role of AP-2α during cancer treatment and progression (migration and invasion). We have data suggesting that migration is, at least in part, regulated by secreted factors. By performing a whole genome microarray analysis of the tumor cells expressing AP-2α siRNA we identified several AP-2α-regulated genes involved in apoptosis and migration such as FAST kinase, osteopontin, caspase 9, members of the TNF family, laminin alpha 1, collagen type XII, alpha 1 and adam. INTRODUCTION The AP-2 family of transcription factors consist of five closely related proteins of Mr 50,000, AP-2a, b, g , d and e (Feng and Williams, 2003; Hilger-Eversheim et al., 2000; Zhao et al., 2001) encoded by distinct genes. These transcription factors can form homo- or heterodimers via helix-span-helix motifs and transactivate their target genes by binding to GC-rich consensus sequences in the promoter regions (Williams and Tjian, 1991). AP-2 factors orchestrate a variety of cell processes including apoptosis, cell growth, cell