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.

Terrinoni, A., Pagani, I., Zucchi, I., Chiaravalli, A., Serra, V., Rovera, F., et al. (2011). OTX1 expression in breast cancer is regulated by p53. ONCOGENE, 30(27), 3096-3103 [10.1038/onc.2011.31].

OTX1 expression in breast cancer is regulated by p53

Terrinoni, A;MELINO, GENNARO;
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.
Pubblicato
Rilevanza internazionale
Abstract
Esperti anonimi
Settore BIO/11
eng
Breast Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Otx Transcription Factors; Tumor Suppressor Protein p53
Terrinoni, A., Pagani, I., Zucchi, I., Chiaravalli, A., Serra, V., Rovera, F., et al. (2011). OTX1 expression in breast cancer is regulated by p53. ONCOGENE, 30(27), 3096-3103 [10.1038/onc.2011.31].
Terrinoni, A; Pagani, I; Zucchi, I; Chiaravalli, A; Serra, V; Rovera, F; Sirchia, S; Dionigi, G; Miozzo, M; Frattini, A; Ferrari, A; Capella, C; Pasquali, F; Curto, F; Albertini, A; Melino, G; Porta, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/131864
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