Identification of pigment epithelium-derived factor as a direct target of the p53 family member genes.
p63 and p73 show a high degree of structural homology to p53 and are members of a family of transcriptional factors that can activate transcription of p53-responsive genes. p53 is mutated in more than 50% of human cancers, whereas p63 and p73 are rarely mutated. Studies of knockout mice also revealed an unexpected functional diversity among the p53 family. To determine how p63 and p73 are involved in tumorigenesis and normal development, we used cDNA microarray to examine 9216 genes in human colorectal cancer cells. We discovered that the expression of pigment epithelium-derived factor (PEDF) was specifically induced by either p63 or p73, but not by p53. We also report here that the PEDF gene contains a response element specific for p63 and p73 in its promoter region and is a direct target of p63 and p73. Collectively, p63 and p73 may be involved in cell fate by inducing PEDF expression.
Sasaki
Yasushi
Y
Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan.
Naishiro
Yasuyoshi
Y
Oshima
Yuichiro
Y
Imai
Kohzoh
K
Nakamura
Yusuke
Y
Tokino
Takashi
T
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms; D004268:DNA-Binding Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009414:Nerve Growth Factors / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D015843:Serpins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D000099174:Pigment Epithelium-Derived Factor
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015843:Serpins; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000099174:Pigment Epithelium-Derived Factor; C115051:TP63 protein, human; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse