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

doi:10.1038/sj.onc.1204999

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	87-95
Number of pages	9
Journal	Oncogene
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/sj.onc.1204999
State	Published - Jan 3 2002
Externally published	Yes

Keywords

Adenovirus
Anti-sense
Glioblastoma
Invasion
Urokinase plasminogen receptor

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

Online availability

10.1038/sj.onc.1204999

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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

Adachi, Y, Chandrasekar, N, Kin, Y, Lakka, SS, Mohanam, S, Yanamandra, N, Mohan, PM, Fuller, GN, Fang, B, Fueyo, J, Dinh, DH, Olivero, WC, Tamiya, T, Ohmoto, T, Kyritsis, AP & Rao, JS 2002, 'Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense upar and sense p16 gene sequences', Oncogene, vol. 21, no. 1, pp. 87-95. https://doi.org/10.1038/sj.onc.1204999

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

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.",

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

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AU - Adachi, Yoshiaki

AU - Chandrasekar, Nirmala

AU - Kin, Yoshiaki

AU - Lakka, Sajani S.

AU - Mohanam, Sanjeeva

AU - Yanamandra, Niranjan

AU - Mohan, Pamarthi M.

AU - Fuller, Gregory N.

AU - Fang, Bingliang

AU - Fueyo, Juan

AU - Dinh, Dzung H.

AU - Olivero, William C.

AU - Tamiya, Takashi

AU - Ohmoto, Takashi

AU - Kyritsis, Anthanassios P.

AU - Rao, Jasti S.

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N2 - 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.

AB - 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.

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

Abstract

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