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  • Oncogenomics
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PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation

Oncogene volume 26, pages 7921–7932 (2007)Cite this article

Abstract

Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of oral squamous-cell carcinoma (OSCC), cell lines for genomic copy-number aberrations by array-CGH using our in-house arrays, we identified a 3-Mb homozygous deletion at 10p12 in 1 of 18 cell lines (5.6%). Among seven genes located within this region, expression of PRTFDC1 mRNA was not detected in 50% (9/18) or decreased in 5.6% (1/18) of OSCC cell lines, but detected in normal oral epithelia and restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2′-deoxycytidine. Among 17 cell lines without a homozygous deletion, the hypermethylation of the PRTFDC1 CpG island, which showed promoter activity, was observed in all nine cell lines with no or reduced PRTFDC1 expression (52.9%). Methylation of this CpG island was also observed in primary OSCC tissues (8/47, 17.0%). In addition, restoration of PRTFDC1 in OSCC cells lacking its expression inhibited cell growth in colony-formation assays, whereas knockdown of PRTFDC1 expression in OSCC cells expressing the gene promoted cell growth. These results suggest that epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis.

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Acknowledgements

We are grateful to Professor Yusuke Nakamura (Human Genome Center, The Institute of Medical Science, The University of Tokyo) for his continuous encouragement throughout this work. We thank Ai Watanabe, Ayako Takahashi and Rumi Mori for technical assistance. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas (C) and 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and by a Grant-in-Aid from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST).

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Authors and Affiliations

  1. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan

    E Suzuki, I Imoto, A Pimkhaokham, T Nakagawa, K-i Kozaki & J Inazawa

  2. Department of Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

    E Suzuki & T Amagasa

  3. Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan

    I Imoto, K-i Kozaki & J Inazawa

  4. Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), Saitama, Japan

    I Imoto, K-i Kozaki & J Inazawa

  5. Department of Oral & Maxillofacial surgery, Faculty of Dentistry, Chulalongkorn University, Patumwan, Bangkok, Thailand

    A Pimkhaokham

  6. Division of Cervico-Gnathostomatology, Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan

    N Kamata

  7. 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone,

    J Inazawa

  8. , Tokyo Medical and Dental University, Tokyo, Japan

    J Inazawa

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  1. E Suzuki
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Correspondence to J Inazawa.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Suzuki, E., Imoto, I., Pimkhaokham, A. et al. PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation. Oncogene 26, 7921–7932 (2007). https://doi.org/10.1038/sj.onc.1210589

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