Work

Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT‐LacZ×Apc1638N mice

Year: 2011

Type: article

Abstract: ABSTRACT The Wnt pathway is a pivotal signaling cascade in colorectal carcinogenesis. The purpose of this work is to determine whether depletion of folate and other metabolically related B vitamins induces in vivo activation of intestinal Wnt signaling and whether this occurs in parallel with increased tumorigenesis. A hybrid mouse was created by crossing a Wnt ‐reporter animal ( BAT‐LacZ ) with a model of colorectal cancer ( Apc1638N ). A mild depletion of folate and vitamins B 2 , B 6 , and B 12 was induced over 16 wk, and the control animals in each instance were pair fed a diet containing the basal requirement of these nutrients. The multiplicity of macroscopic tumors and aberrant crypt foci both increased by ~50% in the hybrid mice fed the depletion diet ( P <0.05). A 4‐fold elevation in Wnt signaling was produced by the depletion diet ( P <0.05) and was accompanied by significant changes in the expression of a number of Wnt ‐related genes in a pattern consistent with its activation. Proliferation and apoptosis of the colonic mucosa both changed in a protransformational direction ( P <0.05). In summary, mild depletion of multiple B vitamins produces in vivo activation of colonic Wnt signaling, implicating it as a key pathway by which B‐vitamin inadequacies enhance intestinal tumorigenesis.—Liu, Z., Ciappio, E. D., Crott, J. W., Brooks, R. S., Nesvet, J., Smith, D. E., Choi, S.‐W., Mason, J. B. Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT‐LacZ×Apc1638N mice. FASEB J. 25, 3136‐3145 (2011). www.fasebj.org

Source: The FASEB Journal

DOI: 10.1096/fj.11-184143