AP-2
proteins are a family of developmentally-regulated
transcription factors. They are encoded by five different genes (alpha, beta, gamma, delta, and epsilon) but they share a common structure. AP-2 plays relevant roles in growth, differentiation, and adhesion by controlling the transcription of specific genes. Evidence shows that the AP-2 genes are involved in
tumorigenesis and for instance, they act as
tumor suppressors in
melanomas and mammary
carcinomas. Here we investigated the function of the AP-2alpha
protein in
cancer formation and progression focusing on apoptosis and migration. We introduced AP-2alpha-specific
siRNA (as oligos or in retroviruses) in HeLa or MCF-7 human
tumor cells and obtained a pronounced down-modulation of AP-2a
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-2a 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-2alpha
siRNA, we identified several AP-2alpha-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.