SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer

DOI PDF PubMed 被引用文献3件 参考文献48件
  • Satoshi Ida
    1Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
  • Nobuyuki Ozaki
    2Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Kimi Araki
    1Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
  • Kotaro Hirashima
    3Department of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
  • Yoko Zaitsu
    4Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Katsunobu Taki
    1Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
  • Yasuo Sakamoto
    2Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Yuji Miyamoto
    2Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Eiji Oki
    4Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Masaru Morita
    4Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Masayuki Watanabe
    5Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Yoshihiko Maehara
    4Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Ken-ichi Yamamura
    1Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
  • Hideo Baba
    2Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Masaki Ohmuraya
    1Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.

書誌事項

公開日
2015-07-13
資源種別
journal article
DOI
  • 10.1158/1541-7786.mcr-14-0581
公開者
American Association for Cancer Research (AACR)

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説明

<jats:title>Abstract</jats:title> <jats:p>Colorectal cancer is a major cause of deaths due to cancer; therefore, research into its etiology is urgently needed. Although it is clear that chronic inflammation is a risk factor for colorectal cancer, the details remain uncertain. Serine protease inhibitor, Kazal type 1 (SPINK1) is mainly produced in pancreatic acinar cells. However, SPINK1 is expressed in various cancers and in inflammatory states, such as colon cancer and inflammatory bowel disease. There are structural similarities between SPINK1 and epidermal growth factor (EGF). Hence, it was hypothesized that SPINK1 functions as a growth factor for tissue repair in inflammatory states, and if prolonged, acts as a promoter for cell proliferation in cancerous tissues. Here, immunohistochemical staining for SPINK1 was observed in a high percentage of colorectal cancer patient specimens and SPINK1 induced proliferation of human colon cancer cell lines. To clarify its role in colon cancer in vivo, a mouse model exposed to the colon carcinogen azoxymethane and nongenotoxic carcinogen dextran sodium sulfate revealed that Spink3 (mouse homolog of SPINK1) is overexpressed in cancerous tissues. In Spink3 heterozygous mice, tumor multiplicity and tumor volume were significantly decreased compared with wild-type mice. These results suggest that SPINK1/Spink3 stimulates the proliferation of colon cancer cells and is involved in colorectal cancer progression.</jats:p> <jats:p>Implications: Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer. Mol Cancer Res; 13(7); 1130–8. ©2015 AACR.</jats:p>

収録刊行物

  • Molecular Cancer Research

    Molecular Cancer Research 13 (7), 1130-1138, 2015-07-13

    American Association for Cancer Research (AACR)

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