title: The AP-2alpha transcription factor regulates tumor cell migration and apoptosis.
abstract: 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.
authors: Institute for Cancer Research and Treatment (IRCC), Department of Oncology Science, University of Torino, Str. Prov. 142-Km 3.95, 10060 Candiolo (To), Italy.
authors: Francesca
authors: F
authors: Orso
authors: Michela
authors: M
authors: Fassetta
authors: Elisa
authors: E
authors: Penna
authors: Alessandra
authors: A
authors: Solero
authors: Katia
authors: K
authors: De Filippo
authors: Piero
authors: P
authors: Sismondi
authors: Michele
authors: M
authors: De Bortoli
authors: Daniela
authors: D
authors: Taverna
mesh_terms: D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D050656:Transcription Factor AP-2