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Sonic hedgehog relates to colorectal carcinogenesis

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Aim

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.

Methods

Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.

Results

Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.

Conclusion

This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.

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Abbreviations

Shh:

Sonic hedgehog

Ptch:

Patched

Smo:

Smoothened

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Acknowledgments

This study was supported by the grant of Cancer Research Project Cooperated by TAIHO Pharmaceutical Co., Ltd. and The University of Tokushima.

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Authors and Affiliations

  1. Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Tokushima, 770-8503, Japan

    Kozo Yoshikawa, Mitsuo Shimada, Hidenori Miyamoto, Jun Higashijima, Tomohiko Miyatani, Masanori Nishioka, Nobuhiro Kurita & Takashi Iwata

  2. Department of Molecular and Environmental Pathology, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Tokushima, 770-8503, Japan

    Hisanori Uehara

Authors
  1. Kozo Yoshikawa
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  2. Mitsuo Shimada
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  3. Hidenori Miyamoto
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  4. Jun Higashijima
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  5. Tomohiko Miyatani
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  6. Masanori Nishioka
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  7. Nobuhiro Kurita
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  8. Takashi Iwata
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  9. Hisanori Uehara
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Corresponding author

Correspondence to Mitsuo Shimada.

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Yoshikawa, K., Shimada, M., Miyamoto, H. et al. Sonic hedgehog relates to colorectal carcinogenesis. J Gastroenterol 44, 1113–1117 (2009). https://doi.org/10.1007/s00535-009-0110-2

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  • DOI: https://doi.org/10.1007/s00535-009-0110-2

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