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Alterations of Fas (APO-1/CD 95) gene and its relationship with p53 in non small cell lung cancer

Oncogene volume 20, pages 6632–6637 (2001)Cite this article

Abstract

The Fas (APO-1/CD95) system regulates a number of physiological and pathological processes of cell death. The ligand for Fas induces apoptosis by interacting with a transmembrane cell surface Fas receptor. The key role of the Fas system has been studied mostly in the immune system, but Fas mutations, one of the possible mechanisms for resistance to apoptosis signaling, may be involved in the pathogenesis of non-lymphoid malignancies as well. To better understand the potential involvement of Fas system in non-small cell lung cancer (NSCLC) we evaluated Fas and Fas-ligand mRNA expression by polymerase chain reaction in 102 tumor samples and in 44 normal surrounding tissues. Although over 60% of the human NSCLC analysed expressed both genes, they seem to be unable to induce apoptosis in vivo by autocrine suicide. In this regard, we investigated in 79 cases, the promoter and the entire coding region of the Fas gene by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing for detecting putative alterations. Sixteen tumors (20.25 %) were found to have Fas alterations, in promoter and/or exon region. In all cases samples carried heterozygous alterations and mostly showed simultaneous mutations of p53 gene. Moreover, the quantitative analysis of Fas mRNA expression showed high levels of Fas messenger associated with p53 wild-type status alone. Taken together, these findings point to an involvement of Fas/Fas-ligand system in the development of NSCLC, suggesting that the loss of its apoptotic function might be linked to p53 alterations which contribute to the self-maintenance of cancer cells.

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Acknowledgements

This work has been supported by grants from the Associazione Italiana per 1a Ricerca sul Cancro (A.I.R.C.).

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Authors and Affiliations

  1. Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Italy

    Laura Boldrini, Pinuccia Faviana, Francesca Pistolesi, Silvia Gisfredi, Dagmar Di Quirico, Fulvio Basolo & Gabriella Fontanini

  2. Department of Cardio-Thoracic Surgery, University of Pisa, Italy

    Marco Lucchi, Alfredo Mussi & Carlo Alberto Angeletti

  3. Department of Oncology, U.O. of Cytogenetic and Molecular Genetic, Pisa, 56100, Italy

    Fulvia Baldinotti, Antonella Fogli & Paolo Simi

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  1. Laura Boldrini
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  13. Gabriella Fontanini
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Correspondence to Gabriella Fontanini.

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Boldrini, L., Faviana, P., Pistolesi, F. et al. Alterations of Fas (APO-1/CD 95) gene and its relationship with p53 in non small cell lung cancer. Oncogene 20, 6632–6637 (2001). https://doi.org/10.1038/sj.onc.1204727

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