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Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells

Implication of the tumor suppressor genes for gene therapy

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Summary

Human (U251, U87, U343) and rat glioma cell lines (C6, 9L) were examined by the reverse transcriptase-polymerase chain reaction and subsequent nucleotide sequencing analysis to see whether they express wild type (wt)-p53 or mutated form (mut)-p53 messages. Results showed that U87, U343, and C6 cells expressed wt-p53 messages whereas U251 and 9L cells expressed mut-p53 messages. All these cell lines were transfected with wt-p53 cDNA or the s-myc gene linked to the mouse mammary tumor virus (MMTV) promoter. Of several G418-resistant clones obtained from each transfection, a few expressed the s-Myc or wt-p53 proteins. Independent of mutations in the intrinsic p53 gene, the cellular growthin vitro and tumorigenicity in nude mice of these clones were drastically suppressed, the extent of suppression being correlated with the expression level of the transfected gene. Flow-cytometric analysis demonstrated that both p53 and s-Myc arrested the cell cycle at the G1/S boundary. These data suggest that these genes having negative effects on tumor cell proliferation could be used in gene therapy of gliomas, which are caused by alteration of the p53 gene or by some other genetic change.

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Authors and Affiliations

  1. Biophysics Division, National Cancer Center Research Institute, Tokyo

    Akio Asai, Yohei Miyagi, Akinori Sugiyama, Michiko Gamanuma, Seok Il Hong & Yoshiyuki Kuchino

  2. Second Department of Pathology, Yokohama City University, Yokohama

    Yohei Miyagi

  3. Department of Clinical Pathology, Korea Cancer Center Hospital, Seoul, Korea

    Seok Il Hong

  4. Department of Transfusion Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo

    Shigeru Takamoto

  5. Department of Neurosurgery, National Cancer Center Hospital, Tokyo

    Kazuhiro Nomura

  6. Department of Neurosurgery, University of Tokyo, Tokyo

    Akio Asai

  7. Department of Neurosurgery, Tokyo Women's Medical College, Tokyo

    Kintomo Takakura

  8. Department of Neurosurgery, Saitama Medical College, Moroyama, Japan

    Masao Matsutani

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  1. Akio Asai
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  2. Yohei Miyagi
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  3. Akinori Sugiyama
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  4. Michiko Gamanuma
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  5. Seok Il Hong
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  6. Shigeru Takamoto
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  7. Kazuhiro Nomura
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  8. Masao Matsutani
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  9. Kintomo Takakura
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  10. Yoshiyuki Kuchino
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Asai, A., Miyagi, Y., Sugiyama, A. et al. Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells. J Neuro-Oncol 19, 259–268 (1994). https://doi.org/10.1007/BF01053280

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  • DOI: https://doi.org/10.1007/BF01053280

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