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Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1

Oncogene volume 20, pages 869–873 (2001)Cite this article

Abstract

Alpha-fetoprotein (AFP) producing gastric cancer (AFP–GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, HNF1 (hapatocyte nuclear factor 1) and a repressive transcription factor, ATBF1 (AT motif binding factor 1). RNase protection assays revealed that the production of AFP in gastric cancer cells did not directly associate with HNF1 expression. An inverse relation between the expressions of ATBF1 and AFP was clearly observed in gastric cancer cells. CAT assays showed the direct inhibition of AFP gene expression by ATBF1. Methylation analysis of the AFP promoter region in gastric cancer cells suggested that methylation itself could not explain the silencing of the AFP gene. Immunohistochemistry of resected clinical samples revealed that AFP producing cells lacked ATBF1 immunoreactivity. Our data suggests that the absence of ATBF1 is responsible for AFP gene expression in gastric cancer, and the absence of ATBF1 is a distinct characteristic of AFP-GC and might be important for its highly malignant nature.

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Abbreviations

AFP:

Alpha-Fetoprotein

AFP-GC:

Alpha-Fetoprotein producing gastric cancer

ATBF1:

AT motif binding factor 1

HNF1:

hepatocyte nuclear factor 1

CAT:

chloramphenicol acetyltransferase

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Acknowledgements

The authors thank Dr Masanori Terashima for providing ISt-1. We also thank Manami Yamamoto and Yukimi Itoh for technical assistance. This work was supported by a research grant from the Scientific Research Fund of the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. First Department of Internal Medicine, Nagoya City University Medical School Nagoya, 467-8601, Japan

    Hiromi Kataoka, Takashi Joh, Kyoji Seno & Makoto Itoh

  2. Department of Bioregulation Research, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuhi-ku, Nagoya, 467-8601, Japan

    Yutaka Miura, Kiyofumi Asai & Taiji Kato

  3. Department of Pathology, Nagoya City University School of Nursing, 1 Kawasumi, Mizuho-cho, Mizuhi-ku, Nagoya, 467-8601, Japan

    Toyohiro Tada

  4. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, T2N 4N1, Calgary, Alberta, Canada

    Taiki Tamaoki

  5. Department of Biochemistry, Hokkaido University School of Medicine, Sapporo, 060, Japan

    Hidekazu Nakabayashi

  6. Department of Pathology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan

    Makoto Kawaguchi

Authors
  1. Hiromi Kataoka
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  2. Yutaka Miura
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Kataoka, H., Miura, Y., Joh, T. et al. Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1. Oncogene 20, 869–873 (2001). https://doi.org/10.1038/sj.onc.1204160

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