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Identification of pigment epithelium-derived factor as a direct target of the p53 family member genes

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Abstract

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.

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Acknowledgements

We thank Dr Joseph F Costello for valuable discussion in this study. This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (YS, KI and TT).

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Author notes

  1. Yasushi Sasaki and Yasuyoshi Naishiro: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, 060-8556, Sapporo, Japan

    Yasushi Sasaki, Yasuyoshi Naishiro, Yuichiro Oshima & Takashi Tokino

  2. First Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, 060-8543, Sapporo, Japan

    Kohzoh Imai

  3. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan

    Yusuke Nakamura

Authors
  1. Yasushi Sasaki
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  2. Yasuyoshi Naishiro
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  3. Yuichiro Oshima
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  4. Kohzoh Imai
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  5. Yusuke Nakamura
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  6. Takashi Tokino
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Correspondence to Takashi Tokino.

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Sasaki, Y., Naishiro, Y., Oshima, Y. et al. Identification of pigment epithelium-derived factor as a direct target of the p53 family member genes. Oncogene 24, 5131–5136 (2005). https://doi.org/10.1038/sj.onc.1208695

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  • DOI: https://doi.org/10.1038/sj.onc.1208695

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