Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 3
Figure 2

References

  • Basilico C and Moscatelli D . (1992). Adv. Cancer Res., 59, 115–165.

  • Bastaki M, Nelli EE, Dell'Era P, Rusnati M, Molinari-Tosatti MP, Parolini S, Auerbach R, Ruco LP, Possati L and Presta M . (1997). Arterioscl. Thromb. Vasc. Biol., 17, 454–464.

  • Carmeliet P . (2000). Nat. Med., 6, 389–395.

  • Dell'Era P, Belleri M, Stabile H, Massardi ML, Ribatti D and Presta M . (2001). Oncogene, 20, 2655–2663.

  • Dell'Era P, Coco L, Ronca R, Sennino B and Presta M . (2002). Oncogene, 21, 2433–2440.

  • Diede SJ and Gottschling DE . (1999). Cell, 99, 723–733.

  • Folkman J . (1995). Nat. Med., 1, 27–31.

  • Giavazzi R, Giuliani R, Coltrini D, Bani MR, Ferri C, Sennino B, Tosatti MP, Stoppacciaro A and Presta M . (2001). Cancer Res., 61, 309–317.

  • Glienke J, Schmitt AO, Pilarsky C, Hinzmann B, Weiss B, Rosenthal A and Thierauch KH . (2000). Eur. J. Biochem., 267, 2820–2830.

  • Hanahan D and Folkman J . (1996). Cell, 86, 353–364.

  • Hubscher U, Nasheuer HP and Syvaoja JE . (2000). Trends Biochem. Sci., 25, 143–147.

  • Hughes P, Tratner I, Ducoux M, Piard K and Baldacci G . (1999). Nucleic Acids Res., 27, 2108–2114.

  • Kahn J, Mehraban F, Ingle G, Xin X, Bryant JE, Vehar G, Schoenfeld J, Grimaldi CJ, Peale F, Draksharapu A, Lewin DA and Gerritsen ME . (2000). Am. J. Pathol., 156, 1887–1900.

  • Karthikeyan R, Vonarx EJ, Straffon AF, Simon M, Faye G and Kunz BA . (2000). J. Mol. Biol., 299, 405–419.

  • Larson RS and Springer TA . (1990). Immunol. Rev., 114, 181–217.

  • Lehman IR and Kaguni LS . (1989). J. Biol. Chem., 264, 4265–4268.

  • Liekens S, De Clercq E and Neyts J . (2001). Biochem. Pharmacol., 61, 253–270.

  • Liu L, Mo J, Rodriguez-Belmonte EM and Lee MY . (2000). J. Biol. Chem., 275, 18739–18744.

  • Ohsaka A, Takagi S, Takeda A, Katsura Y, Takahashi K and Matsuoka T . (2001). Inflamm. Res., 50, 270–274.

  • Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS and Martin GR . (1992). Lab. Invest., 67, 519–528.

  • Podust VN, Chang LS, Ott R, Dianov GL and Fanning E . (2002). J. Biol. Chem., 277, 3894–3901.

  • Roland I, Minet E, Ernest I, Pascal T, Michel G, Remacle J and Michiels C . (2000). Eur. J. Biochem., 267, 3567–3574.

  • Sola F, Gualandris A, Belleri M, Giuliani R, Coltrini D, Bastaki M, Tosatti MP, Bonardi F, Vecchi A, Fioretti F, Ciomei M, Grandi M, Mantovani A and Presta M . (1997). Angiogenesis, 1, 102–116.

  • St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B and Kinzler KW . (2000). Science, 289, 1197–1202.

  • Sugino A . (1995). Trends Biochem. Sci., 20, 319–323.

  • Takagi S, Takahashi K, Katsura Y, Matsuoka T and Ohsaka A . (2000). Acta Haematol., 103, 78–83.

  • Waga S and Stillman B . (1994). Nature, 369, 207–212.

  • Waga S and Stillman B . (1998). Annu. Rev. Biochem., 67, 721–751.

  • Wang JL, Liu YH, Lee MC, Nguyen TM, Lee C, Kim A and Nguyen M . (2000). Microvasc. Res., 59, 394–397.

  • Wu SM, Zhang P, Zeng XR, Zhang SJ, Mo J, Li BQ and Lee MY . (1998). J Biol. Chem., 273, 9561–9569.

  • Yang CL, Chang LS, Zhang P, Hao H, Zhu L, Toomey NL and Lee MY . (1992). Nucleic Acids Res., 20, 735–745.

  • Zeng XR, Hao H, Jiang Y and Lee MY . (1994). J. Biol. Chem., 269, 24027–24033.

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marco Presta.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208359

Keywords

  • FGF2
  • DNA polymerase
  • endothelium
  • angiogenesis

Further reading

Search

Quick links