title: OTX1 expression in breast cancer is regulated by p53.
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.
authors.affiliation: Biochemistry Laboratory, IDI-IRCCS, c/o Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Terrinoni
authors.forename: I S
authors.initials: IS
authors.lastname: Pagani
authors.forename: I
authors.initials: I
authors.lastname: Zucchi
authors.forename: A M
authors.initials: AM
authors.lastname: Chiaravalli
authors.forename: V
authors.initials: V
authors.lastname: Serra
authors.forename: F
authors.initials: F
authors.lastname: Rovera
authors.forename: S
authors.initials: S
authors.lastname: Sirchia
authors.forename: G
authors.initials: G
authors.lastname: Dionigi
authors.forename: M
authors.initials: M
authors.lastname: Miozzo
authors.forename: A
authors.initials: A
authors.lastname: Frattini
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.forename: C
authors.initials: C
authors.lastname: Capella
authors.forename: F
authors.initials: F
authors.lastname: Pasquali
authors.forename: F Lo
authors.initials: FL
authors.lastname: Curto
authors.forename: F L
authors.initials: FL
authors.lastname: Curto
authors.forename: A
authors.initials: A
authors.lastname: Albertini
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.forename: G
authors.initials: G
authors.lastname: Porta
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051857:Otx Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: C497655:OTX1 protein, human; D051857:Otx Transcription Factors; D016159:Tumor Suppressor Protein p53