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Involvement of PTEN/Akt signaling in capsular invasive carcinomas developed in a rat two-stage thyroid carcinogenesis model after promotion with sulfadimethoxine

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Abstract

Purpose

Rat thyroid follicular cell carcinomas invading into the thyroid capsule are highly produced by promotion with sulfadimethoxine (SDM) in a rat two-stage thyroid carcinogenesis model. In this study, we investigated the participation of phosphoinositide 3-kinase (PI3K) signaling pathway that is associated with malignant phenotypes of many cancers on the development of SDM-induced capsular invasive carcinomas.

Methods

Thyroid proliferative lesions developed 10 or 15 weeks after promotion with SDM in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine were immunohistochemically analyzed with regard to cellular distribution of phosphatase and tensin homolog (PTEN) and Akt isoforms, as well as their downstream molecules.

Results

Increased expression of PI3K signaling molecules was evident in association with the development of lesion stages from the early focal hyperplasia to the late carcinomas. Capsular carcinomas, and the less frequent parenchymal carcinomas, exclusively expressed phosphorylated, inactive PTEN, and active Akt isoforms, as did their downstream molecules. Among the Akt isoforms, enhanced expression of Akt1 was more prominent than that of Akt2 in both capsular and parenchymal carcinomas.

Conclusions

Activation of the PI3K pathway through phosphorylation of PTEN promotes the high production of capsular carcinomas as well as the development of less frequent parenchymal carcinomas.

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Acknowledgments

We thank Mrs. Shigeko Suzuki for her technical assistance in preparing histological specimens.

Conflict of interest statement

All authors disclose that there are no conflicts of interest that could inappropriately influence the outcome of the present study.

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Authors and Affiliations

  1. Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan

    Sayaka Kemmochi, Kunitoshi Mitsumori & Makoto Shibutani

  2. Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Sayaka Kemmochi

  3. Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Hitoshi Fujimoto, Gye-Hyeong Woo, Kaoru Inoue, Miwa Takahashi, Akiyoshi Nishikawa & Makoto Shibutani

  4. Food Safety Commission, Akasaka Park Bld. 22nd F. Akasaka 5-2-20, Minato-ku, Tokyo, 100-8989, Japan

    Masao Hirose

Authors
  1. Sayaka Kemmochi
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  2. Hitoshi Fujimoto
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  3. Gye-Hyeong Woo
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  4. Kaoru Inoue
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  5. Miwa Takahashi
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  6. Kunitoshi Mitsumori
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  7. Masao Hirose
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  9. Makoto Shibutani
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Corresponding author

Correspondence to Makoto Shibutani.

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Kemmochi, S., Fujimoto, H., Woo, GH. et al. Involvement of PTEN/Akt signaling in capsular invasive carcinomas developed in a rat two-stage thyroid carcinogenesis model after promotion with sulfadimethoxine. J Cancer Res Clin Oncol 137, 723–732 (2011). https://doi.org/10.1007/s00432-010-0931-7

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  • DOI: https://doi.org/10.1007/s00432-010-0931-7

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