OTX1 expression in breast cancer is regulated by p53

• DOI: 10.1038/onc.2011.31
• Publication Date: 2011-04-11T10:19:50Z
• Authors: 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
• Keywords: cancer stem cells; human breast cancer; p53; Neoplastic; Settore BIO/11 - BIOLOGIA MOLECOLARE; 0303 health sciences; Otx Transcription Factors; 572; CML; MRD; LSC; gDNA; real time PCR; CML, MRD, LSC, gDNA, real time PCR; Breast Neoplasms; 3. Good health; OTX1; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Gene Expression Regulation; Humans; Female; Tumor Suppressor Protein p53; cancer stem cells; human breast cancer; OTX1; p53; Breast Neoplasm; Otx Transcription Factor; Human; Breast Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Otx Transcription Factors; Tumor Suppressor Protein p53

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.