Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice

Hachimine,Daisaku; Uchida,Kazushige; Asada,Masanori; Nishio,Akiyoshi; Kawamata,Seiji; Sekimoto,Go; Murata,Miki; Yamagata,Hideo; Yoshida,Katsunori; Mori,Shigeo; Tahashi,Yoshiya; Matsuzaki,Koichi; Okazaki,Kazuichi

doi:10.3892/ijo.32.6.1221

June 2008 Volume 32 Issue 6

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June 2008 Volume 32 Issue 6

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Article

Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice

Authors:
- Daisaku Hachimine
- Kazushige Uchida
- Masanori Asada
- Akiyoshi Nishio
- Seiji Kawamata
- Go Sekimoto
- Miki Murata
- Hideo Yamagata
- Katsunori Yoshida
- Shigeo Mori
- Yoshiya Tahashi
- Koichi Matsuzaki
- Kazuichi Okazaki
View Affiliations / Copyright

Affiliations: Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan
Pages: 1221-1226
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Published online on: June 1, 2008

https://doi.org/10.3892/ijo.32.6.1221
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Abstract

Chronic inflammation predisposes to cancer. Transforming growth factor (TGF)-β, a multifunctional protein, suppresses the growth of normal colonic epithelial cells, whereas it stimulates the proliferation of cancer cells. Interleukin (IL)-10-deficient mice, which develop colitis and colorectal cancer, show an increased level of plasma TGF-β. Although TGF-β may be a key molecule in the development of colon cancer arising from chronic colitis in IL-10-deficient mice, the role of TGF-β still remains unclear. TGF-β activates not only TGF-β type I receptor (TβRI) but also c-Jun N-terminal kinase (JNK), which converts the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). We studied C57BL/6-IL-10-deficient mice (n=18) at 4 to 32 weeks of age. We investigated histology, and pSmad2/3L, pSmad2/3C, and p53 by immunohistochemistry. pSmad3L staining was detected in the cancer cells in all 10 mice with colonic cancer and in the epithelial cells in 7 of 12 mice with colonic dysplasia, but not in the normal or colitic mice. pSmad3c was detected without any significant difference between stages. p53 was weakly stained in a few cancer cells in 5 out of 10 mice. Smad3L signaling plays an important role in the carcinogenesis of chronic colitis in IL-10-deficient mice.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice

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