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.

journal_name

Oncogene

journal_title

Oncogene

authors

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

doi

10.1038/onc.2011.31

subject

Has Abstract

pub_date

2011-07-07 00:00:00

pages

3096-103

issue

27

eissn

0950-9232

issn

1476-5594

pii

onc201131

journal_volume

30

pub_type

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