Regulation of CTEN expression by p53 and ΔNp63α
Date Issued
2016
Date
2016
Author(s)
Chen, Ya-chi
Abstract
p53, the guardian of genome, is involved in cell cycle arrest and apoptosis to maintain the stability of genome in cellular stress. p63, a member of the p53 transcriptional factor family, is a master of regulation of epithelial homeostasis and development. ΔNp63α, one of p63 isoforms, enhances the ability of cell adhesion. Our previous study revealed that ΔNp63α binds to putative p53 binding sites present in CTEN promoter and transcriptionally regulates CTEN expression involved in prostate cell adhesion. Furthermore, CTEN and p63 down-regulation correlates with prostate cancer progression from primary tumors to metastatic lesions. Therefore, we hypothesize that overexpression of ΔNp63α might enhance CTEN expression and hamper prostate cancer cell progression. In our study, overexpression of ΔNp63α in prostate cancer cells induced the mRNA and protein levels of CTEN. However the increases are slight. We assume that there might be other transcription factors or co-activators involved in the regulation of CTEN gene expression in prostate cancer cells in addition to exogenously expressed ΔNp63α. On the other hand, we found that p53 down-regulates CTEN promoter activity whether ΔNp63α exists or not. Also, overexpression of p53 decreased CTEN mRNA and protein in non-malignant prostate cell line, RWPE-1. By using the chromatin immunoprecipitation (ChIP) assay, we demonstrated that p53 binds to CTEN promoter within the region between -80 to +25. Moreover, by using cisplatin to induce DNA damage and celluar stress, we discovered that cisplatin exposure caused increased p53 and decreased the mRNA and protein levels of CTEN. In conclusion, our findings reveal that p53 binds to the CTEN promoter region which also recognized by ΔNp63α. p53 repressed the expression of CTEN in response to DNA damage stress.
Subjects
CTEN
p53
DNp63alpha
SDGs
Type
thesis