OTX1 expression in breast cancer is regulated by p53

A. Terrinoni, I. S. Pagani, I. Zucchi, A. M. Chiaravalli, V. Serra, F. Rovera, S. Sirchia, G. Dionigi, M. Miozzo, A. Frattini, A. Ferrari, C. Capella, F. Pasquali, F. L. Curto, A. Albertini, G. Melino, G. Porta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3096-3103
Number of pages8
JournalOncogene
Volume30
Issue number27
DOIs
Publication statusPublished - Jul 7 2011

Keywords

  • cancer stem cells
  • human breast cancer
  • OTX1
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Terrinoni, A., Pagani, I. S., Zucchi, I., Chiaravalli, A. M., Serra, V., Rovera, F., Sirchia, S., Dionigi, G., Miozzo, M., Frattini, A., Ferrari, A., Capella, C., Pasquali, F., Curto, F. L., Albertini, A., Melino, G., & Porta, G. (2011). OTX1 expression in breast cancer is regulated by p53. Oncogene, 30(27), 3096-3103. https://doi.org/10.1038/onc.2011.31