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Association of Gankyrin and Stemness Factor Expression in Human Colorectal Cancer

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Abstract

Background

It is widely accepted that the adenoma-carcinoma sequence represents the process by which most colorectal cancers (CRCs) arise. Although gankyrin is overexpressed in CRC tissues, its roles in the initiation step of colorectal carcinogenesis remain largely unexplored.

Aim

We investigated the expression of gankyrin and stemness factors in human colorectal adenomas, precancerous lesions, as well as CRC tissues to assess its involvement in colorectal carcinogenesis.

Methods

Expression of several molecules including gankyrin and certain stemness factors was compared in 50 pairs of adenoma and surrounding normal mucosa using real-time quantitative polymerase chain reaction and in 30 CRC tissues using immunohistochemistry.

Results

In CRC specimens, expression of CD133, a cancer stem cell marker, was significantly correlated with gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal cancer cells. Expression of gankyrin and these stemness factors was significantly higher in adenomas than in the surrounding normal mucosa. Importantly, a significant correlation was observed between the expression of gankyrin, VEGF, and Nanog in colorectal adenomas.

Conclusion

In CRC development, gankyrin would control stem cell behavior by regulating the expression of stemness factors.

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Abbreviations

CRC:

Colorectal cancer

VEGF:

Vascular endothelial growth factor

LST:

Laterally spreading tumor

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Acknowledgments

We thank Dr. Yoshie O and Munakata H (Kinki University) for technical assistance and helpful suggestions. This research was supported by grants from the Yasuda Medical Foundation, Novartis Foundation and Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Hiromasa Mine, Toshiharu Sakurai, Hiroshi Kashida, Shigenaga Matsui, Naoshi Nishida, Tomoyuki Nagai, Satoru Hagiwara & Masatoshi Kudo

  2. Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Tomohiro Watanabe

Authors
  1. Hiromasa Mine
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  2. Toshiharu Sakurai
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  3. Hiroshi Kashida
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  4. Shigenaga Matsui
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  5. Naoshi Nishida
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  6. Tomoyuki Nagai
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  7. Satoru Hagiwara
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  8. Tomohiro Watanabe
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  9. Masatoshi Kudo
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Correspondence to Toshiharu Sakurai or Masatoshi Kudo.

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Mine, H., Sakurai, T., Kashida, H. et al. Association of Gankyrin and Stemness Factor Expression in Human Colorectal Cancer. Dig Dis Sci 58, 2337–2344 (2013). https://doi.org/10.1007/s10620-013-2627-8

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  • DOI: https://doi.org/10.1007/s10620-013-2627-8

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