The AP-2alpha transcription factor regulates tumor cell migration and apoptosis.
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.
Orso
Francesca
F
Institute for Cancer Research and Treatment (IRCC), Department of Oncology Science, University of Torino, Str. Prov. 142-Km 3.95, 10060 Candiolo (To), Italy.
Fassetta
Michela
M
Penna
Elisa
E
Solero
Alessandra
A
De Filippo
Katia
K
Sismondi
Piero
P
De Bortoli
Michele
M
Taverna
Daniela
D
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*
D034741:RNA, Small Interfering; D050656:Transcription Factor AP-2