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  • Original Paper
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Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis

Abstract

Angiogenin is an angiogenic protein that undergoes nuclear translocation in endothelial cells where it accumulates in the nucleolus and stimulates rRNA transcription, a rate-limiting step in ribosome biogenesis, protein translation, and cell growth. Here, we report that angiogenin is required for cell proliferation induced by various other angiogenic proteins including acidic and basic fibroblast growth factors (aFGF and bFGF), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF). Downregulation of angiogenin in endothelial cells by small interfering RNA (siRNA) and antisense results in a decrease in rRNA transcription, ribosome biogenesis, and cell proliferation induced by these angiogenic factors. Inhibitors of the nuclear translocation of angiogenin abolish the angiogenic activities of these factors. Stable angiogenin antisense transfection in HeLa cells reduces tumor angiogenesis in athymic mice despite the elevated expression level of bFGF and VEGF. Thus, nuclear angiogenin assumes an essential role in endothelial cell proliferation and is necessary for angiogenesis induced by other angiogenic factors. Angiogenin-stimulated rRNA transcription in endothelial cells may thus serve as a crossroad in the process of angiogenesis induced by various angiogenic factors.

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References

  • Adams SA and Subramanian V . (1999). Angiogenesis, 3, 189–199.

  • Au S, Weiner N and Schacht J . (1986). Antimicrob. Agents Chemother., 30, 395–397.

  • Barton DP, Cai A, Wendt K, Young M, Gamero A and De Cesare S . (1997). Clin. Cancer Res., 3, 1579–1586.

  • Bergers G and Benjamin LE . (2003). Nat. Rev. Cancer, 3, 401–410.

  • Bicknell R and Vallee BL . (1988). Proc. Natl. Acad. Sci. USA, 85, 5961–5965.

  • Bodner-Adler B, Hefler L, Bodner K, Leodolter S, Frischmuth K, Kainz C and Mayerhofer K . (2001). Anticancer Res., 21, 809–812.

  • Eberle K, Oberpichler A, Trantakis C, Krupp W, Knupfer M, Tschesche H and Seifert V . (2000). Anticancer Res., 20, 1679–1684.

  • Fett JW, Strydom DJ, Lobb RR, Alderman EM, Bethune JL, Riordan JF and Vallee BL . (1985). Biochemistry, 24, 5480–5486.

  • Folkman J . (2002). Cancer Cell, 1, 113–115.

  • Folkman J . (2003). Curr. Mol. Med., 3, 643–651.

  • Fu X, Roberts WG, Nobile V, Shapiro R and Kamps MP . (1999). Growth Factors, 17, 125–137.

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

  • Homer JJ, Greenman J and Stafford ND . (2002). Clin. Otolaryngol., 27, 32–37.

  • Hu G-F . (1998). Proc. Natl. Acad. Sci. USA, 95, 9791–9795.

  • Hu G-F, Chang SI, Riordan JF and Vallee BL . (1991). Proc. Natl. Acad. Sci. USA, 88, 2227–2231.

  • Hu G-F and Riordan JF . (1993). Biochem. Biophys. Res. Commun., 197, 682–687.

  • Hu G-F, Riordan JF and Vallee BL . (1994). Proc. Natl. Acad. Sci. USA, 91, 12096–12100.

  • Hu G-F, Riordan JF and Vallee BL . (1997). Proc. Natl. Acad. Sci. USA, 94, 2204–2209.

  • Hu G-F, Strydom DJ, Fett JW, Riordan JF and Vallee BL . (1993). Proc. Natl. Acad. Sci. USA, 90, 1217–1221.

  • Hu G-F, Xu C and Riordan JF . (2000). J. Cell. Biochem., 76, 452–462.

  • Imaizumi T, Itaya H, Nasu S, Yoshida H, Matsubara Y, Fujimoto K, Matsumiya T, Kimura H and Satoh K . (2000). Thromb. Haemost., 83, 949–955.

  • Kinoshita M and Shimokado K . (1999). Arterioscler. Thromb. Vasc. Biol., 19, 2323–2329.

  • Kushlinskii NE, Babkina IV, Solov́ev YN and Trapeznikov NN . (2000). Bull. Exp. Biol. Med., 130, 691–693.

  • Li D, Bell J, Brown A and Berry CL . (1994). J. Pathol., 172, 171–175.

  • Liu S, Yu D, Xu ZP, Riordan JF and Hu G-F . (2001). Biochem. Biophys. Res. Commun., 287, 305–310.

  • Moenner M, Gusse M, Hatzi E and Badet J . (1994). Eur. J. Biochem., 226, 483–490.

  • Montero S, Guzman C, Cortes-Funes H and Colomer R . (1998). Clin. Cancer Res., 4, 2161–2168.

  • Moroianu J and Riordan JF . (1994). Proc. Natl. Acad. Sci. USA, 91, 1677–1681.

  • Olson KA, Byers HR, Key ME and Fett JW . (2001). Clin. Cancer Res., 7, 3598–3605.

  • Olson KA, Byers HR, Key ME and Fett JW . (2002). Int. J. Cancer, 98, 923–929.

  • Olson KA, Fett JW, French TC, Key ME and Vallee BL . (1995). Proc. Natl. Acad. Sci. USA, 92, 442–446.

  • Papetti M and Herman IM . (2002). Am. J. Physiol. Cell Physiol., 282, C947–C970.

  • Polakowski IJ, Lewis MK, Muthukkaruppan VR, Erdman B, Kubai L and Auerbach R . (1993). Am. J. Pathol., 143, 507–517.

  • Ribatti D, Vacca A and Presta M . (2002). Gen. Pharmacol., 35, 227–231.

  • Risau W . (1996). Cancer Met. Rev., 15, 149–151.

  • Ruggero D and Pandolfi PP . (2003). Nat. Rev. Cancer, 3, 179–192.

  • Ruschoff J, Plate K, Bittinger A and Thomas C . (1989). Pathol. Res. Pract., 185, 878–885.

  • Shimoyama S, Gansauge F, Gansauge S, Oohara T, Kaminishi M and Beger HG . (1999). Pancreas, 18, 225–230.

  • Shimoyama S, Shimizu N, Tsuji E, Yamasaki K, Kawahara M and Kaminishi M . (2002). Anticancer Res., 22, 1045–1052.

  • Trere D, Pession A and Derenzini M . (1989). Exp. Cell Res., 184, 131–137.

  • Ugurel S, Rappl G, Tilgen W and Reinhold U . (2001). J. Clin. Oncol., 19, 577–583.

  • Williams PD, Bennett DB, Gleason CR and Hottendorf GH . (1987). Antimicrob. Agents Chemother., 31, 570–574.

  • Wilting J, Christ B and Bokeloh M . (1991). Anat. Embryol., 183, 259–271.

  • Xu ZP, Tsuji T, Riordan JF and Hu G-F . (2002). Biochem. Biophys. Res. Commun., 294, 287–292.

  • Xu ZP, Tsuji T, Riordan JF and Hu G-F . (2003). Biochemistry, 42, 121–128.

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Acknowledgements

We thank Drs BL Vallee and JF Riordan for advice and discussion. This work was supported by NIH Grant CA91086 and by the Endowment for Research in Human Biology, Inc.

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Correspondence to Guo-fu Hu.

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Kishimoto, K., Liu, S., Tsuji, T. et al. Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis. Oncogene 24, 445–456 (2005). https://doi.org/10.1038/sj.onc.1208223

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