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Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to γ-radiation-induced thymic lymphoma

Oncogene volume 25, pages 2022–2029 (2006)Cite this article

Abstract

The Fas death receptor is a cell surface molecule involved in apoptosis as well as in proliferative or activating signals of many cells types, including T lymphocytes. Using quantitative real-time reverse transcription–PCR analysis, we confirm that expression of this gene is scarcely perceptible in thymic lymphomas induced by γ-irradiation in C57BL/6J mice. Notably, we also demonstrate for the first time that Fas expression is significantly upregulated in vivo both after single high dose of radiation and in thymic lymphoma-free mice. In addition, we determined its levels of expression in five mouse strains exhibiting different degrees of susceptibility (SPRET/Ei, SEG/Pas, BALB/cJ, C57BL/6J and RF/J). Interestingly, we found the highest levels of expression in SPRET/Ei and SEG/Pas strains (both derived from the Mus spretus species), which are known to have the most resistant phenotype, and the lowest levels in the most susceptible strains C57BL/6J and RF/J. DNA sequencing of the Fas promoter in all five strains showed many polymorphisms that can be classified into three functional haplotypes by using luciferase assays: (1) C57BL/6J and RF/J, (2) BALB/cJ and (3) SPRET/Ei and SEG/Pas. Promoter activities in response to single high doses of radiation correlated well with the levels of Fas expression and are consistent with the degree of strain susceptibility.

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Acknowledgements

We thank L González, M Matabuena, M Guerrero, MJ Bueno and R Peregil for aid with animals, P Fernández for helping with statistical analysis and E Pérez-Gómez for technical assistance. We are also grateful to Professor A Morales for critical reading of the manuscript. This work was supported by grants from the European Commission (EURATOM Work Programme 2003, FI6R-CT-2003-508842 to JS), ‘Ministerio de Educación y Ciencia’ (SAF2003-05048) and ‘Ministerio de Salud y Consumo’ (Lymphoma Network, G03/179) to JF-P. MV-M is the recipient of a predoctoral fellowship from ‘Ministerio de Educación y Ciencia’ (FPU AP2002-0294).

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  1. Departamento de Biología, Laboratorio de Genética Molecular Humana, Universidad Autónoma de Madrid, Madrid, Spain

    M Villa-Morales, J Santos & J Fernández-Piqueras

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  1. M Villa-Morales
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  2. J Santos
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  3. J Fernández-Piqueras
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Correspondence to J Fernández-Piqueras.

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Villa-Morales, M., Santos, J. & Fernández-Piqueras, J. Functional Fas (Cd95/Apo-1) promoter polymorphisms in inbred mouse strains exhibiting different susceptibility to γ-radiation-induced thymic lymphoma. Oncogene 25, 2022–2029 (2006). https://doi.org/10.1038/sj.onc.1209234

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