RRC ID 48848
Author Tanikawa C, Zhang YZ, Yamamoto R, Tsuda Y, Tanaka M, Funauchi Y, Mori J, Imoto S, Yamaguchi R, Nakamura Y, Miyano S, Nakagawa H, Matsuda K.
Title The Transcriptional Landscape of p53 Signalling Pathway.
Journal EBioMedicine
Abstract Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53+/+ or p53-/- mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53+/+ mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas) database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53+/+ mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.
Volume 20
Pages 109-119
Published 2017-6-1
DOI 10.1016/j.ebiom.2017.05.017
PII S2352-3964(17)30215-3
PMID 28558959
PMC PMC5478243
MeSH Animals Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism Computational Biology DNA Damage Gene Expression Profiling Gene Expression Regulation* High-Throughput Nucleotide Sequencing Humans Mice Mice, Knockout RNA Splicing Signal Transduction* Transcription, Genetic* Transcriptome Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism*
IF 5.736
Times Cited 17
Mice RBRC01361