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  • Original Paper
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Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells

Oncogene volume 18, pages 2189–2199 (1999)Cite this article

Abstract

The CD95 (Fas/APO-1) system regulates a number of physiological and pathological processes of cell death. The ligand for CD95 induces apoptosis in sensitive target cells by interacting with a transmembrane cell surface CD95 receptor. We previously reported that the recombinant adenovirus-mediated transfer of the wild-type p53 gene caused apoptotic cell death in a variety of human cancer cells. To better understand the mechanism responsible for this cell death signaling, we have investigated the potential involvement of the CD95 receptor/ligand system in p53-mediated apoptosis. The transient expression of the wild-type p53 gene up-regulated the CD95 ligand mRNA as well as protein expression in H1299 human lung cancer cells deficient for p53 and in DLD-1 and SW620 human colon cancer cells with mutated p53, all of which constitutively expressed CD95 receptor as shown by a flow cytometric analysis, and induced rapid apoptotic cell death as early as 24 h after gene transfer. However, the sensitivity to the cytolytic effect of agonistic anti-CD95 antibody (CH11) varied among these cell lines: CH11 induced apoptosis in H1299 cells, but not in DLD-1 and SW620 cells despite their abundant CD95 receptor expression, suggesting that the CD95 receptors on DLD-1 and SW620 cells might be inactivated. In addition, an antagonistic anti-CD95 ligand antibody (4H9) that interfered with the CD95-receptor-ligand interaction partially reduced the apoptosis induced by the wild-type p53 gene transfer in H1299 cells, whereas apoptosis of DLD-1 and SW620 cells occurred in the presence of 4H9. Taken together, these findings led us to conclude that the CD95 receptor/ligand system is differentially involved in p53-mediated apoptosis, suggesting that the restoration of the wild-type p53 function may mediate apoptosis through CD95 receptor/ligand interactions as well as an alternative pathway.

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Abbreviations

IGF-BP:

insulin-like growth factor-binding protein

CD95-L:

CD95 ligand

CMV:

cytomegalovirus

NSCLC:

non-small cell lung cancer

MOI:

multiplicity of infection

RT-PCR:

reverse transcription-PCR

ICE:

interleukin 1β-converting enzyme

FAP-1:

Fas-associated phosphatase-1

FITC:

fluorescein isothiocyanate

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Acknowledgements

We thank Dr Hideo Yagita (Department of Immunology, Juntendo University School of Medicine, Tokyo) for providing a CD95-L-transfected cell line and anti-CD95-L antibody. We also thank Tohru Tanida for technical support and Satomi Segawa for preparing the manuscript. This work was supported in part by grants from the Ministry of Education, Science, and Culture, Japan; by grants from the Ministry of Health and Welfare, Japan (Health Sciences Research Grants (Research on Human Genome and Gene Therapy)); by grants from the National Cancer Institutes and the National Institutes of Health (RO1CA45187) [JAR]; (Specialized Program of Research Excellence [SPORE] in Lung Cancer [P50-CA70907]); by gifts to the Devision of Surgery and Anesthesiology from Tenneco and Exxon for the Core Laboratory Facility; by the UTMD. Anderson Cancer Center Support Core Grant (CA16672); by a grant from the Mathers Foundation; and a sponsored research agreement with Introgen Therapeutics.

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Authors and Affiliations

  1. Section of Molecular Oncology, Okayama University Medical School, Okayama, 700, Japan

    Takuya Fukazawa, Toshiyoshi Fujiwara, Yoshinori Morimoto, Jianghua Shao, Masahiko Nishizaki & Yoshihiko Kadowaki

  2. First Department of Surgery, Okayama University Medical School, Okayama, 700, Japan

    Takuya Fukazawa, Toshiyoshi Fujiwara, Yoshinori Morimoto, Jianghua Shao, Masahiko Nishizaki, Yoshihiko Kadowaki, Akio Hizuta & Noriaki Tanaka

  3. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Laurie B Owen-Schaub

  4. Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Jack A Roth

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Fukazawa, T., Fujiwara, T., Morimoto, Y. et al. Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells. Oncogene 18, 2189–2199 (1999). https://doi.org/10.1038/sj.onc.1202561

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