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Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy

Oncogene volume 27, pages 4233–4241 (2008)Cite this article

Abstract

Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk of breast cancer. In the present study we aimed to unravel the transcriptional control of Brip1 and to determine its expression levels in a set of 101 primary invasive breast carcinomas. Transcription of Brip1 was found to be cell growth-related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved E2F-responsive site. Repression of Brip1 expression by the cell growth-inhibiting compound 1α,25-dihydroxyvitamin D3 depended on this same E2F-responsive site. In spite of its role as a tumor suppressor, both quantitative reverse transcriptase-PCR analyses and immunohistochemical stainings showed significantly elevated Brip1 expression levels in grade 3 tumors as compared to grade 1 or 2 carcinomas. Furthermore, increased Brip1 transcript levels were found in tumors with an estrogen receptor-negative, progesterone receptor-negative or HER-2-positive status. In conclusion, these data show that Brip1 is a genuine target gene for the E2F/Rb pathway and that elevated expression levels of Brip1 are detected in primary invasive breast carcinomas with unfavorable characteristics.

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Acknowledgements

We thank Ine Beullens, Mark Van Camp, Suzanne Marcelis, Biauw Keng Tan and Laura Kozak for excellent technical assistance and Dr JR Nevins and Dr J Magae for providing materials. This work is supported by grants from the Fund for Scientific Research (FWO-G.0508.05 and FWO-G0553.06) and the KU Leuven Research Council (EF/05/007 SymBioSys). GE is a postdoctoral fellow for the Fund for Scientific Research (FWO). The authors have no conflict of interest.

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Authors and Affiliations

  1. Laboratorium voor Experimentele Geneeskunde en Endocrinologie (LEGENDO), Katholieke Universiteit Leuven, Leuven, Belgium

    G Eelen, L Verlinden, R Bouillon & A Verstuyf

  2. Department of Pathology, University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium

    I Vanden Bempt & M Drijkoningen

  3. Multidisciplinary Breast Center, University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium

    M Drijkoningen, A Smeets, P Neven & M R Christiaens

  4. CMPG/ESAT, Katholieke Universiteit Leuven, Leuven, Belgium

    K Marchal

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  1. G Eelen
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Correspondence to A Verstuyf.

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Eelen, G., Vanden Bempt, I., Verlinden, L. et al. Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy. Oncogene 27, 4233–4241 (2008). https://doi.org/10.1038/onc.2008.51

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