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Expression of the intestine-specific transcription factors, Cdx1 and Cdx2, correlates shift to an intestinal phenotype in gastric cancer cells

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Abstract

Purpose

It is well known that gastric cancers (GCs) at early stages, independent of the histological type, mainly consist of gastric phenotype malignant cells, while those at advanced stage tend to have a more intestinal phenotype with progression. However, the connection between this shift and expression of homeobox genes, which are important factors to maintain tissue character, has remained unclear. We therefore evaluated the expression of Cdx1/2 in relation to the phenotype of GCs.

Methods

We analyzed the expression of Cdx1/2 mRNAs by Northern blotting and Cdx2 protein by immunohistochemistry in seventy advanced GCs, and evaluated phenotypically using mucin- and immunohistochemistry.

Results

Seventy GCs were divided phenotypically into 16 gastric (G type), 18 gastric and intestinal mixed (GI type), 18 intestinal (I type), and 18 null (N type) phenotypes, independent of the histological classification. Cdx1 and Cdx2 mRNAs statistically demonstrated an increase with shift from G to I (P=0.042 and P=0.0082, respectively). Cdx2 nuclear staining was observed immunohistochemically in the intestinal phenotypic cancer cells, but could not be detected in those with only the gastric phenotype.

Conclusions

These results show that Cdx1 and Cdx2 might be indispensable for intestinal phenotypic expression even in gastric cancer cells.

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Acknowledgments

The authors thank Dr. Malcolm A. Moore for revision of the scientific English language and Ms. Hisayo Ban, Ms. Michiyo Tominaga, and Ms. Sachiko Tokumasu for expert technical assistance. This study was supported in part by a Grant-in-Aid for the Millennium Genome Project, a Grant-in-Aid for the Second-term Comprehensive 10-year Strategy for Cancer Control and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The Cdx1 and Cdx2 expression vectors were generous gifts from Dr. Juan Lucio Iovanna, Centre de Recherche, INSERM, Marseille, France.

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Authors and Affiliations

  1. Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, 464-8681, Nagoya, Japan

    Tsutomu Mizoshita, Ken-ichi Inada, Tetsuya Tsukamoto, Koji Nozaki & Masae Tatematsu

  2. Department of Internal Medicine and Bioregulation, Nagoya City University Medical School, Nagoya, Japan

    Tsutomu Mizoshita, Takashi Joh & Makoto Itoh

  3. Division of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan

    Yoshitaka Yamamura

  4. Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan

    Toshikazu Ushijima

  5. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan

    Shigeo Nakamura

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  1. Tsutomu Mizoshita
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  2. Ken-ichi Inada
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  3. Tetsuya Tsukamoto
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  7. Yoshitaka Yamamura
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  8. Toshikazu Ushijima
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  9. Shigeo Nakamura
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  10. Masae Tatematsu
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Corresponding author

Correspondence to Masae Tatematsu.

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Mizoshita, T., Inada, Ki., Tsukamoto, T. et al. Expression of the intestine-specific transcription factors, Cdx1 and Cdx2, correlates shift to an intestinal phenotype in gastric cancer cells. J Cancer Res Clin Oncol 130, 29–36 (2004). https://doi.org/10.1007/s00432-003-0503-1

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  • DOI: https://doi.org/10.1007/s00432-003-0503-1

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