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OTX1 expression in breast cancer is regulated by p53

Oncogene volume 30, pages 3096–3103 (2011)Cite this article

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An Erratum to this article was published on 06 March 2014

A Corrigendum to this article was published on 07 July 2011

Abstract

The p53 transcription factor has a critical role in cell stress response and in tumor suppression. Wild-type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation. It has been recently demonstrated that wild-type p53 has developmental and differentiation functions. Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding self-renewal of cancer stem cells (CSCs) and instead promoting their differentiation. In this study, 28 human breast carcinomas have been analyzed for expression of wild-type p53 and of a pool of non-clustered homeobox genes. We demonstrated that orthodenticle homolog 1 gene (OTX1) is transcribed in breast cancer. We established that the p53 protein directly induces OTX1 expression by acting on its promoter. OTX1 has been described as a critical molecule for axon refinement in the developing cerebral cortex of mice, and its activity in breast cancer suggests a synergistic function with p53 in CSC differentiation. Wild-type p53 may regulate cellular differentiation by an alternative pathway controlling OTX1 signaling only in breast cancer cells and not in physiological conditions.

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Acknowledgements

We thank Centro Grandi Strumenti University of Insubria, Fondazione Comunitaria del Varesotto- ONLUS, Ministero dell’Istruzione, dell’Università e della Ricerca DM25591 and Banca del Monte di Lombardia, Pavia, Italy to GP. This work has also been supported by the Medical Research Council, UK; ‘Alleanza contro il Cancro’ (ACC12-ACC6), MIUR/PRIN (RBIP06LCA9_0023), AIRC (2008-2010_33-08), Italian Human ProteomeNet RBRN07BMCT_007 and Telethon (GGPO9133) to GM, Ministero della Salute RF06-RF07 to GM. GP thanks to AIL Varese.

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Authors and Affiliations

  1. c/o Department of Experimental Medicine and Biochemical Sciences, Biochemistry Laboratory, IDI-IRCCS, University of Rome ‘Tor Vergata’, Rome, Italy

    A Terrinoni, V Serra & G Melino

  2. Department of Experimental and Clinical Biomedical Sciences, Università dell’Insubria, Varese, Italy

    I S Pagani, F Pasquali, F L Curto & G Porta

  3. Institute of Biomedical Technologies, National Research Council, Milan, Italy

    I Zucchi, A Frattini & A Albertini

  4. Department of Pathology, Ospedale di Circolo, Varese, Italy

    A M Chiaravalli

  5. Department of Surgical Sciences, University of Insubria, Varese, Italy

    F Rovera

  6. Department of Medicine, Surgery and Dentistry, Medical Genetics Unit, Universita’ degli Studi di Milano, Milano, Italy

    S Sirchia & M Miozzo

  7. Department of Surgical Sciences, Endocrine Surgery Research Center, University of Insubria, Varese, Italy

    G Dionigi

  8. Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy

    A Ferrari

  9. Department of Human Morphology, Anatomic Pathology Unit, Centro Insubre di Biotecnologie per la Salute Umana, Ospedale di Circolo, University of Insubria, Varese, Italy

    C Capella

  10. Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Leicester, UK

    G Melino

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  1. A Terrinoni
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Correspondence to G Porta.

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Supplementary Information accompanies the paper on the Oncogene website

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Terrinoni, A., Pagani, I., Zucchi, I. et al. OTX1 expression in breast cancer is regulated by p53. Oncogene 30, 3096–3103 (2011). https://doi.org/10.1038/onc.2011.31

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