Details

Autor(en) / Beteiligte

• Brooks, Ryan S
• Ciappio, Eric D
• Bennett, Grace
• Crott, Jimmy W
• Mason, Joel B
• Liu, Zhenhua

Titel

TNF‐α induced alterations in the Wnt signaling cascade: a potential mechanism for obesity‐associated colorectal tumorigenesis

Ist Teil von

• The FASEB journal, 2010-04, Vol.24 (S1), p.lb384-lb384

Ort / Verlag

Federation of American Societies for Experimental Biology

Erscheinungsjahr

2010

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Epidemiological studies consistently implicate obesity as an important risk factor for several types of cancer, and the data is particularly compelling for colorectal cancer. However, the underlying mechanism is not defined. This study investigated whether Wnt‐signaling, a critical pathway in colorectal carcinogenesis, is upregulated by the inflammatory cytokine, TNF‐α, which has been found to be elevated in obesity. Obesity was induced in C57BL6 mice using a high‐fat diet (60% kcal). TNF‐α protein in the colon, determined by ex vivo culture of the colon followed by ELISA of the media, was significantly elevated (p<0.05) in obese mice. Phospho‐GSK3β, which is an important intermediary in Wnt signaling and which has been reported to be induced by TNF‐α, was elevated by immunohistochemistry in the colonic mucosa of obese mice. Significant elevations of β‐catenin protein as well as increased c‐myc mRNA were evident in the colonic mucosa of the obese mice (p<0.05), and are also consistent with Wnt activation. These results demonstrate that obesity elevates colonic levels of TNF‐α and provide evidence that it may activate Wnt‐signaling in that organ. (This material is based on work supported by the USDA under agreement no. 58‐1950‐7‐707 and by the Prevent Cancer Foundation)