Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense upar and sense p16 gene sequences

Yoshiaki Adachi, Nirmala Chandrasekar, Yoshiaki Kin, Sajani S. Lakka, Sanjeeva Mohanam, Niranjan Yanamandra, Pamarthi M. Mohan, Gregory N. Fuller, Bingliang Fang, Juan Fueyo, Dzung H. Dinh, William C. Olivero, Takashi Tamiya, Takashi Ohmoto, Anthanassios P. Kyritsis, Jasti S. Rao

Research output: Contribution to journalArticle

Abstract

Our previous studies showed that the urokinase-type plasminogen activator receptor (uPAR) and the p16 tumor suppressor gene play a significant role in glioma invasion. We expected that downregulation of uPAR and overexpression of p16 using a bicistronic vector might cause a additive and cooperative effect in the suppression of glioma invasion and growth. The bicistronic construct (Ad-uPAR/p16)-infected glioblastoma cell lines had significantly lower levels of uPAR and higher levels of p16 than controls. Cell cycle analysis showed the bicistronic vector caused G0/G1 arrest of the cell cycle. In vitro glioblastoma cell growth and invasiveness were inhibited in Ad-uPAR/p16-infected cells compared with controls. Ad-uPAR/p16 suppressed the tumor growth of glioblastoma cell lines in an ex vivo intracerebral tumor model and an in vivo subcutaneous tumor model. Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalOncogene
Volume21
Issue number1
DOIs
StatePublished - Jan 3 2002

Keywords

  • Adenovirus
  • Anti-sense
  • Glioblastoma
  • Invasion
  • Urokinase plasminogen receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Adachi, Y., Chandrasekar, N., Kin, Y., Lakka, S. S., Mohanam, S., Yanamandra, N., Mohan, P. M., Fuller, G. N., Fang, B., Fueyo, J., Dinh, D. H., Olivero, W. C., Tamiya, T., Ohmoto, T., Kyritsis, A. P., & Rao, J. S. (2002). Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense upar and sense p16 gene sequences. Oncogene, 21(1), 87-95. https://doi.org/10.1038/sj.onc.1204999