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Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma

Oncogene volume 20, pages 1678–1687 (2001)Cite this article

Abstract

The transcription factor E2F1 is a key component of cell cycle that acts to transactivate genes required for S phase entry. Thus, it plays an important role in cellular proliferation, oncogenesis and differentiation. In order to investigate its potential implication in human lung carcinogenesis, we studied E2F1 protein expression by Western blotting and immunohistochemistry in a series of 58 human lung tumours of all histological types. We showed that E2F1 product was overexpressed in 92% (24/26) of small cell lung carcinoma (SCLC) and in 50% (5/10) of large cell neuroendocrine carcinoma (LCNEC) whereas it was undetectable in 90% (10/11) of adenocarcinoma and 82% (9/11) of squamous carcinoma when compared to corresponding normal lung. No amplification was found but an increase in E2F1 mRNA expression was detected in 75% (18/24) of SCLC overexpressing E2F1 product. In these tumours and in contrast with NSCLC, upregulation of E2F1 product was associated with its nuclear accumulation and with overexpression of several of its target-genes. Moreover, E2F1 overexpression in NE lung tumours was significantly associated with a high KI67 index (P<0.0001) as well as a Bcl-2:Bax ratio >1 (P<0.001). Overall, these results demonstrate a distinct pattern of E2F1 expression in human lung tumours and suggest that its deregulation could be involved in the carcinogenesis of SCLC.

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Acknowledgements

This work was supported by grants from the Association pour la Recherche sur le Cancer, from the Comité Départemental de la Ligue contre le Cancer de l'Isère and from the Groupement des Entreprises Francaises dans la Lutte contre le Cancer. B Eymin was supported by INSERM (Poste Accueil).

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  1. Groupe de Recherche sur le Cancer du Poumon, EA 2021, Equipe INSERM 9924, Institut Albert Bonniot, 38706 La Tronche Cedex, France

    Béatrice Eymin, Sylvie Gazzeri, Christian Brambilla & Elisabeth Brambilla

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  1. Béatrice Eymin
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Eymin, B., Gazzeri, S., Brambilla, C. et al. Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma. Oncogene 20, 1678–1687 (2001). https://doi.org/10.1038/sj.onc.1204242

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