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FGF2-induced upregulation of DNA polymerase-δ p12 subunit in endothelial cells

Oncogene volume 24, pages 1117–1121 (2005)Cite this article

Abstract

p12 represents the smallest, so far poorly characterized subunit of the mammalian DNA polymerase δ (polδ) heterotetramer. Previously, to gain a molecular understanding of endothelial cell activation by fibroblast growth factor-2 (FGF2), we identified an upregulated transcript in FGF2-overexpressing murine aortic endothelial cells (FGF2-T-MAE cells) showing 89% identity with human p12. Here, we cloned the open reading frame of the murine p12 cDNA and confirmed the capacity of overexpressed or exogenously added FGF2 to upregulate p12 mRNA and protein in endothelial and NIH3T3 cells with no effect on the other polδ subunits. p12 expression was instead unaffected by serum and different mitogens. Also, anti-p12 antibodies decorated FGF2-T-MAE cell nuclei and their chromosome outline during metaphase. Small interfering RNA-mediated knockdown of p12 caused a significant decrease in FGF2-driven proliferation rate of FGF2-T-MAE cells, in keeping with a modulatory role of p12 in polδ activity. Immunoistochemistry of FGF2-embedded Matrigel plugs and FGF2-overexpressing tumor xenografts demonstrated a nuclear p12 staining of angiogenic CD31+ endothelium. p12 immunoreactivity was also observed in the CD45+/CD11b+ inflammatory infiltrate. Thus, FGF2 upregulates p12 expression in endothelial cells in vitro and in vivo. p12 expression in infiltrating inflammatory cells may suggest additional, cell proliferation-unrelated functions for this polδ subunit.

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Acknowledgements

This work was supported by grants from AIRC, MIUR (Centro di Eccellenza ‘IDET’, Firb 2001, and Cofin 2002), and ISS (Oncotechnological Program) to MP.

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Authors and Affiliations

  1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, viale Europa 11, 25123, Brescia, Italy

    Patrizia Dell'Era, Stefania Nicoli & Marco Presta

  2. IRFMN Mario Negri, Milano, Italy

    Giuseppe Peri

  3. Unit of Biology and Genetics, Department of Sciences Applied to Biosystems, University of Cagliari, Cagliari, Italy

    Mariella Nieddu

  4. Department Cytomorphology, University of Cagliari, Cagliari, Italy

    Maria Grazia Ennas

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  1. Patrizia Dell'Era
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  2. Stefania Nicoli
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  5. Maria Grazia Ennas
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Correspondence to Marco Presta.

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Dell'Era, P., Nicoli, S., Peri, G. et al. FGF2-induced upregulation of DNA polymerase-δ p12 subunit in endothelial cells. Oncogene 24, 1117–1121 (2005). https://doi.org/10.1038/sj.onc.1208359

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