Document Detail


Tumor necrosis factor alpha stimulates invasion of Src-activated intestinal cells.
MedLine Citation:
PMID:  11832448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Src activation is correlated with progression of colorectal cancer (CRC). CRCs accompanied by ulcerative colitis, chronic inflammation in the colon, often have elevated Src activity, and ulcerative colitis-related CRCs are more likely to become invasive, whereas Ras activation is rarely associated with this disease. The aim of this study was to investigate the effects of a proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), on the invasive properties of epithelial cells constitutively expressing activated Ras or Src. METHODS: A cell line derived from intestinal epithelia was transfected with a v-src- or v-H-ras-expressing vector. The effect of TNF-alpha on morphologic changes in colonies cultured in soft agar was determined. Src protein kinase activity, peroxide production, E-cadherin expression levels, and the phosphorylation status of beta-catenin and E-cadherin were determined. The invasive potential of these cells was determined by measuring cell motility and using an in vitro invasion assay. RESULTS: TNF-alpha altered the colony morphology of src-, but not ras-expressing cells. TNF-alpha increased peroxide production, leading to Src protein expression as well as Src activity in src transfectants. Activation of Src by TNF-alpha led to reduced E-cadherin levels and enhanced invasion of src transfectants. Pyrrolidine dithiocarbamate and herbimycin A inhibited these effects. CONCLUSION: These results indicate that Src kinase activation enhances the response of epithelial cells to TNF-alpha leading to increased invasion through mechanisms that involve production of reactive oxygen intermediates.
Authors:
Naoki Kawai; Shingo Tsuji; Masahiko Tsujii; Toshifumi Ito; Masakazu Yasumaru; Yoshimi Kakiuchi; Arata Kimura; Masato Komori; Yutaka Sasaki; Norio Hayashi; Sunao Kawano; Raymond Dubois; Masatsugu Hori
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gastroenterology     Volume:  122     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-08     Completed Date:  2002-03-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-9     Citation Subset:  AIM; IM    
Affiliation:
Graduate School of Medicine, Department of Internal Medicine and Therapeutics, Faculty of Medicine, Osaka University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Agar
Animals
Antineoplastic Agents / pharmacology*
Antioxidants / pharmacology
Cadherins / metabolism
Cell Line, Transformed
Cell Movement / physiology*
Cytoskeletal Proteins / metabolism
Hydrogen Peroxide / metabolism
Intestinal Mucosa / cytology
Neoplasm Invasiveness / physiopathology
Oncogene Protein p21(ras) / genetics,  metabolism
Oncogene Protein pp60(v-src) / genetics,  metabolism*
Oxidative Stress / drug effects,  physiology
Phosphotyrosine / metabolism
Pyrrolidines / pharmacology
Rats
Thiocarbamates / pharmacology
Trans-Activators*
Transfection
Tumor Necrosis Factor-alpha / pharmacology*
Tyrosine / metabolism
beta Catenin
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antioxidants; 0/Cadherins; 0/Catnb protein, rat; 0/Cytoskeletal Proteins; 0/Pyrrolidines; 0/Thiocarbamates; 0/Trans-Activators; 0/Tumor Necrosis Factor-alpha; 0/beta Catenin; 21820-51-9/Phosphotyrosine; 25769-03-3/pyrrolidine dithiocarbamic acid; 55520-40-6/Tyrosine; 7722-84-1/Hydrogen Peroxide; 9002-18-0/Agar; EC 2.7.10.2/Oncogene Protein pp60(v-src); EC 3.6.5.2/Oncogene Protein p21(ras)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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