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AP‐2α and AP‐2γ regulate tumor progression via specific genetic programs
Author(s) -
Orso Francesca,
Penna Elisa,
Cimino Daniela,
Astanina Elena,
Maione Federica,
Valdembri Donatella,
Giraudo Enrico,
Serini Guido,
Sismondi Piero,
De Bortoli Michele,
Taverna Daniela
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-106492
Subject(s) - gene knockdown , biology , rna interference , carcinogenesis , tumor progression , microbiology and biotechnology , cell migration , embryonic stem cell , phenotype , cell growth , cancer research , gene , cell , genetics , rna
The events occurring during tumor formation and progression display similarities to some of the steps in embryonic morphogenesis. The family of AP‐2 proteins consists of five different transcription factors (α, β, γ, δ, and ε) that play relevant roles in embryonic development, as demonstrated by the phenotypes of the corresponding knockout mice. Here, we show that AP‐2α and AP‐2γ proteins play an essential role in tumorigenesis. Down‐modulation of AP‐2 expression in tumor cells by RNA interference (RNAi) led to enhanced tumor growth and reduced chemotherapy‐induced cell death, as well as migration and invasion. Most of these biological modulations were rescued by AP‐2 overexpression. We observed that increased xeno‐transplant growth was mostly due to highly enhanced proliferation of the tumor cells together with reduced innate immune cell recruitment. Moreover, we showed that migration impairment was mediated, at least in part, by secreted factors. To identify the genetic programs involved in tumorigenesis, we performed whole genome microarray analysis of AP‐2α knockdown cells and observed that AP‐2α regulates specific genes involved in cell cycle, cell death, adhesion, and migration. In particular, we showed that ESDN, EREG , and CXCL2 play a major role in AP‐2 controlled migration, as ablation of any of these genes severely altered migration.—Orso, F., Penna, E., Cimino, D., Astanina, E., Maione, F., Valdembri, D., Giraudo, E., Serini, G., Sismondi, P., De Bortoli, M., Taverna, D. AP‐2α and AP‐2γ regulate tumor progression via specific genetic programs. FASEB J. 22, 2702‐2714 (2008)