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Ephrin-A1 promotes the malignant progression of intestinal tumors in Apcmin/+ mice

Oncogene volume 27, pages 3265–3273 (2008)Cite this article

Abstract

The ephrin-A1 and EphA receptors are frequently highly expressed in different human cancers, suggesting that they may promote tumor development and progression. We generated transgenic mice carrying Fabpl4xat-132 ephrin-A1, which express ephrin-A1 in the intestinal epithelial cells. Those mice were then mated with Apcmin/+ mice to produce the compound mice, which overexpress ephrin-A1 in the intestinal tumors of Apcmin/+ mice. We compared the number, size and histopathological features of the intestinal tumors in the Fabpl4xat-132 ephrin-A1/Apcmin/+ compound mice with those of the Apcmin/+ mice. The compound mice showed an increased number of intestinal tumors, significantly in the large intestine, and developed more invasive tumors. Among the 20 mice of each type examined, 5 Apcmin/+ mice developed 5 invasive tumors, 1 invasive tumor in each mouse, in the proximal or middle portions of the small intestine. On the other hand, 14 out of 20 compound mice developed 29 invasive tumors and 16 of them were in the distal small intestine and the large intestine, where transgenic ephrin-A1 was highly expressed. These results suggested that the increased expression of ephrin-A1 accelerated the malignant progression of the intestinal adenoma to invasive tumors.

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Acknowledgements

We thank Drs John F Rawls and Jeffrey I Gordon for providing the pBS-dBam/colon/hGHno 78 vector and Ms Aiko Nakagawa for technical help. This research was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, and University of Tsukuba Research Project.

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Authors and Affiliations

  1. Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    L Shi, F Itoh, S Itoh & M Kato

  2. Departments of Anatomy and Embryology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    S Takahashi

  3. Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan

    M Yamamoto

  4. ERATO Environmental Response Project, Japan Science and Technology Corporation, Tsukuba, Japan

    M Yamamoto

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  1. L Shi
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Correspondence to M Kato.

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

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Shi, L., Itoh, F., Itoh, S. et al. Ephrin-A1 promotes the malignant progression of intestinal tumors in Apcmin/+ mice. Oncogene 27, 3265–3273 (2008). https://doi.org/10.1038/sj.onc.1210992

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