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Contrasting activity of Hedgehog and Wnt pathways according to gastric cancer cell differentiation: relevance of crosstalk mechanisms.

 Jie-Hyun Kim  ;  Hyun Soo Shin  ;  Sang Hun Lee  ;  Inohk Lee  ;  Yeo Song Lee  ;  Jun Chul Park  ;  Yu Jin Kim  ;  Jae Bock Chung  ;  Yong Chan Lee 
 CANCER SCIENCE, Vol.101(2) : 328-335, 2010 
Journal Title
Issue Date
Cell Differentiation ; Cell Line, Tumor ; Hedgehog Proteins/physiology* ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Oncogene Proteins/analysis ; Oncogene Proteins/physiology ; Promoter Regions, Genetic ; Signal Transduction ; Stomach Neoplasms/pathology* ; Trans-Activators/analysis ; Trans-Activators/physiology ; Wnt Proteins/physiology* ; Zinc Finger Protein GLI1 ; beta Catenin/analysis
Gastric cancer displays different biological behaviors according to histological differentiation. The different biological behavior might involve the activation of distinct signaling pathways necessary for the growth and survival of cancer cells in gastric cancer. We investigated the differentiation-related signal interaction between Hedgehog and Wnt pathways in gastric cancer cells. Differentiation of gastric cancer cells was induced by sodium butyrate. The sonic Hedgehog (SHH) signal expressions were increased during cellular differentiation. In contrast, the expression of Wnt signaling was decreased during differentiation. Ectopic expression of glioma-associated oncogene-1 (GLI1) increased the level of secreted frizzled related protein-1 (SFRP1) transcript, whereas inhibition of GLI1 reduced the level of SFRP1 transcript. ChIP assay showed that GLI1 induced the transcriptional regulation of SFRP1 gene expression. Ectopic expression of GLI1 decreased the nuclear beta-catenin staining, but the inhibition of GLI1 induced the reversal of nuclear beta-catenin overexpression. Ectopic expression of beta-catenin also decreased the expression of GLI1 in the butyrate treated cancer cells. SHH and GLI1 immunoexpression was greater in well differentiated gastric cancer tissues compared to poorly differentiated tissues, and nuclear beta-catenin immunoexpression was lower in well differentiated compared to poorly differentiated tissues. The SHH and Wnt pathways are differentially involved according to gastric cancer cell differentiation.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoo Jin(김유진)
Kim, Jie-Hyun(김지현) ORCID logo https://orcid.org/0000-0002-9198-3326
Park, Jun Chul(박준철) ORCID logo https://orcid.org/0000-0001-8018-0010
Lee, Yeo Song(이여송)
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
Chung, Jae Bock(정재복)
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