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Downmodulation of bFGF-binding protein expression following restoration of p53 function

Cancer Gene Therapy volume 8, pages771–782(2001)Cite this article

Abstract

Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector–mediated wild-type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down-regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53-induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein. Cancer Gene Therapy (2001) 8, 771–782

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Acknowledgements

We thank Anton Wellstein for helpful discussion of this manuscript; Ralph Weichselbaum for his kind gift of the SCCHN cell line JSQ-3; Yawen Chiang (formerly at GTI/NOVARTIS and currently at RPR/Aventis) for the adenoviral constructs; Paulette Hubbard for assistance in preparation of this manuscript; the Lombardi Cancer Center's Macromolecular Synthesis and Sequencing Shared Resource, and the Department of Comparative Medicine's animal facility, which are supported in part by US Public Health Service Grant P03 CA51008. This work was supported, in part, by NCI Grant RO1 CA45158 (to E.C.) and the National Foundation for Cancer Research Grant HU 0001 (to E.C.).

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  1. Shigeru Nakai

    Present address: Department of Otolaryngology, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji, Kyoto City, Kyoto, 602, Japan

  2. Zaki A Sherif and Shigeru Nakai: The authors contributed equally to this work.

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  1. Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, 20007, USA

    Zaki A Sherif, Kathleen F Pirollo, Antonina Rait & Esther H Chang

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  1. Zaki A Sherif
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  2. Shigeru Nakai
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Correspondence to Esther H Chang.

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Sherif, Z., Nakai, S., Pirollo, K. et al. Downmodulation of bFGF-binding protein expression following restoration of p53 function. Cancer Gene Ther 8, 771–782 (2001). https://doi.org/10.1038/sj.cgt.7700361

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Keywords

  • p53
  • bFGF-binding protein
  • antiangiogenesis
  • tumor regression

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