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Proliferation-associated Brn-3b transcription factor can activate cyclin D1 expression in neuroblastoma and breast cancer cells

Oncogene volume 27, pages 145–154 (2008) Cite this article

A Correction to this article was published on 09 February 2023

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Abstract

Brn-3b transcription factor enhances proliferation of neuroblastoma (NB) and breast cancer cell lines in vitro and increases the rate and size of in vivo tumour growth, whereas reducing Brn-3b slows growth, both in vitro and in vivo. Brn-3b is elevated in >65% of breast cancer biopsies, and here we demonstrate that Brn-3b is also elevated in NB tumours. We show a significant correlation between Brn-3b and cyclin D1 (CD1) in breast cancers and NB tumours and cell lines. Brn-3b directly transactivates the CD1 promoter in co-transfection experiments, whereas electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrate that Brn-3b protein binds to an octamer sequence located in the proximal CD1 promoter. Site-directed mutagenesis of this sequence resulted in loss of transactivation of the CD1 promoter by Brn-3b. Thus, Brn-3b may act to alter growth properties of breast cancer and NB cells by enhancing CD1 expression in these cells.

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Abbreviations

CD1:

cyclin D1

ChIP:

chromatin immunoprecipitation

EMSA:

electrophoretic mobility shift assay

LTR:

long terminal repeat

NB:

neuroblastoma

POU:

Pit-Oct-Unc

RA:

retinoic acid

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Acknowledgements

We thank Dr Gerard Redeuilh (Paris, France) for cyclin D1 reporter constructs; Dr J Anderson and Dr P Brock (Great Ormond Street Hospital (GOSH), London) for support and discussions; Italian Neuroblastoma Society; Pathology Department (GOSH, London) and UKCCSG, UK for NB RNA or biopsies; Dr D' Arrigo (Guy's Hospital, London) for breast cancer biopsies and Candis Tissue Bank (Liverpool, UK) for RNA from breast cancer. This work was supported by Child Health Research Action Trust (CHRAT); Breast Cancer Campaign (BCC) UK; Association for International Cancer Research (AICR), UK.

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Authors and Affiliations

  1. Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK

    V S Budhram-Mahadeo, S Irshad, S Bowen, S A Lee, L Samady & D S Latchman

  2. Translational Paediatric Oncology, National Institute of Cancer Research (IST), Genoa, Italy

    G P Tonini

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  1. V S Budhram-Mahadeo
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  2. S Irshad
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  3. S Bowen
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  4. S A Lee
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  5. L Samady
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  6. G P Tonini
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  7. D S Latchman
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Correspondence to V S Budhram-Mahadeo.

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Budhram-Mahadeo, V., Irshad, S., Bowen, S. et al. Proliferation-associated Brn-3b transcription factor can activate cyclin D1 expression in neuroblastoma and breast cancer cells. Oncogene 27, 145–154 (2008). https://doi.org/10.1038/sj.onc.1210621

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