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G125A single-nucleotide polymorphism in the human BAX promoter affects gene expression

Oncogene volume 24, pages 2042–2049 (2005)Cite this article

Abstract

Earlier we had reported a guanine to adenosine substitution at position 125 (G125A) in the BAX promoter, and its association with higher stage of the disease and failure to achieve complete response to treatment in chronic lymphocytic leukemia (CLL) patients. The aim of this study was to test the hypothesis that G125A leads to a reduction in the transcription of the BAX gene and that this is a direct cause of altered BAX mRNA and protein expression. In lymphocytes of CLL patients, BAX mRNA expression was determined by RNase protection assay and Bax protein was detected by immunoblotting. The presence of G125A in the BAX promoter was associated with lower BAX mRNA (P=0.004) and protein (P=0.024) levels. In transient expression assays using wild-type and mutant BAX promoter sequences linked to Luciferase as a reporter, the G125A polymorphism reduced expression of the BAX promoter by 2.6-fold. These studies suggest a mechanism for the biological effect of the G125A.

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Acknowledgements

We thank Dr WF Dong for his advice during construction of the pGL3-based plasmids, Ms H Neufeld for assisting with Western blotting experiments, and Mr T Reichert and Ms M Hesson for assisting with preparing illustrations.

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Authors and Affiliations

  1. Department of Pathology, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Canada, S7N 0W8

    Oksana Moshynska & Anurag Saxena

  2. Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada, S7N 5E3

    Igor Moshynskyy

  3. Department of Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada, S7N 5B4

    Igor Moshynskyy & Vikram Misra

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  1. Oksana Moshynska
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  2. Igor Moshynskyy
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Correspondence to Anurag Saxena.

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Moshynska, O., Moshynskyy, I., Misra, V. et al. G125A single-nucleotide polymorphism in the human BAX promoter affects gene expression. Oncogene 24, 2042–2049 (2005). https://doi.org/10.1038/sj.onc.1208377

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