Recombinant adenovirus expressing wild-type p53 is antiangiogenic: A proposed mechanism for bystander effect

Masahiko Nishizaki, Toshiyoshi Fujiwara, Tohru Tanida, Akio Hizuta, Hiroyuki Nishimori, Takashi Tokino, Yusuke Nakamura, Michael Bouvet, Jack A. Roth, Noriaki Tanaka

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalClinical Cancer Research
Volume5
Issue number5
Publication statusPublished - May 1999

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Bystander Effect
Adenoviridae
p53 Genes
Neoplasms
Non-Small Cell Lung Carcinoma
Angiogenesis Inhibitors
Angiogenesis Inducing Agents
Growth
Tumor Suppressor Genes
Vascular Endothelial Growth Factor A
Reverse Transcription
Phenotype
Cell Line
Polymerase Chain Reaction
Messenger RNA
Membranes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Recombinant adenovirus expressing wild-type p53 is antiangiogenic : A proposed mechanism for bystander effect. / Nishizaki, Masahiko; Fujiwara, Toshiyoshi; Tanida, Tohru; Hizuta, Akio; Nishimori, Hiroyuki; Tokino, Takashi; Nakamura, Yusuke; Bouvet, Michael; Roth, Jack A.; Tanaka, Noriaki.

In: Clinical Cancer Research, Vol. 5, No. 5, 05.1999, p. 1015-1023.

Research output: Contribution to journalArticle

Nishizaki, M, Fujiwara, T, Tanida, T, Hizuta, A, Nishimori, H, Tokino, T, Nakamura, Y, Bouvet, M, Roth, JA & Tanaka, N 1999, 'Recombinant adenovirus expressing wild-type p53 is antiangiogenic: A proposed mechanism for bystander effect', Clinical Cancer Research, vol. 5, no. 5, pp. 1015-1023.
Nishizaki, Masahiko ; Fujiwara, Toshiyoshi ; Tanida, Tohru ; Hizuta, Akio ; Nishimori, Hiroyuki ; Tokino, Takashi ; Nakamura, Yusuke ; Bouvet, Michael ; Roth, Jack A. ; Tanaka, Noriaki. / Recombinant adenovirus expressing wild-type p53 is antiangiogenic : A proposed mechanism for bystander effect. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 5. pp. 1015-1023.
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