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 overexpression 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.

Genome‐wide expression profiling and bioinformatics analysis of deregulated genes in human gastric cancer tissue after gastroscopy

“…OTX1 has been described as a critical molecule for neocortex organization and determines progenitor behavior and histogenesis in mammals . In addition, it has been reported that the P53 protein directly induces OTX1 expression by acting on its promoter in breast cancer, and synergistically effected cancer stem cell differentiation . Our data showed the OTX1 mRNA was upregulated in gastric cancer, which has not previously been reported.…”

Expression of VEGF-A, Otx Homeobox and p53 Family Genes in Proliferative Vitreoretinopathy

“…In the control samples, we found basal expression of all genes. In PVR samples, we found little (samples 1, 2, 3, 4, 8, 9, and 10) or no expression (samples 5, 6, 7, 11, and 12) of Otx1, attesting the nondifferentiated state of retinal tissues [23], and variable expressions of VEGF-A, Otx2, Otx3, p53, and p63. We found high Otx3 levels in samples with little levels of Otx2 (samples 3 and 4) (Figure 3).…”

Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis

“…Using gene manipulation, we revealed for the first time the involvement of p53 and Cav-1 in CSC acquisition and cell aggressiveness induced by SWCNTs (Figure 7C, 8A and B). It has been recently demonstrated that wild-type p53 positively regulated cell differentiation in breast cancer cells and loss of p53 favored CSC growth [40,41]. However, the functional role of Cav-1 in CSC induction is not known.…”