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The AP-2a Transcription Factor Regulates Tumor Cell Migration and Apoptosis

  • Francesca Orso
  • Michela Fassetta
  • Elisa Penna
  • Alessandra Solero
  • Katia De Filippo
  • Piero Sismondi
  • Michele De Bortoli
  • Daniela Taverna
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 604)

AP-2 proteins are a family of developmentally-regulated transcription factors. They are encoded by five different genes (α, β, γ, δ, and ε) 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-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.

Keywords

siRNA Oligos Genome Microarray Analysis Laminin Alpha Keratinocyte Specific Gene Apoptotic Cell Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2007

Authors and Affiliations

  • Francesca Orso
    • 1
  • Michela Fassetta
    • 1
  • Elisa Penna
    • 1
  • Alessandra Solero
    • 1
  • Katia De Filippo
    • 1
  • Piero Sismondi
    • 1
  • Michele De Bortoli
    • 1
  • Daniela Taverna
    • 1
  1. 1.Department of Oncology. Science, University of TorinoInstitute for Cancer Research and TreatmentItaly

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