Further upregulation of beta-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of ApcMin/+ mice.
Apc(Min/+) mouse, a mouse model for human familial adenomatosis polyposis, contains a truncating mutation in the Apc gene and spontaneously develops intestinal tumors. Our previous study revealed two distinct stages of tumorigenesis in the colon of Apc(Min/+) mouse: microadenomas and macroscopic tumors. Microadenomas already have lost their remaining allele of the Apc and all microadenomas show accumulation of beta-catenin, indicating that activation of the canonical Wnt pathway is an initiating event in the tumorigenesis. This study shows that expression of nuclear beta-catenin in macroscopic tumors is further upregulated in comparison with that in microadenomas. Furthermore, transcriptional activity of beta-catenin/T-cell factor (Tcf) signaling, assessed using beta-catenin/Tcf reporter transgenic mice, is higher in the macroscopic tumors than that in microadenomas. In addition, the expression level of Dickkopf-1, which is known to be a negative modifier of the canonical Wnt pathway, was reduced only in colon tumors. These results suggest that activation of beta-catenin/Tcf transcription plays a role not only in the initiation stage but also in the promotion stage of colon carcinogenesis in Apc(Min/+) mice.
Oyama
Takeru
T
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Yamada
Yasuhiro
Y
Hata
Kazuya
K
Tomita
Hiroyuki
H
Hirata
Akihiro
A
Sheng
Hongqiang
H
Hara
Akira
A
Aoki
Hitomi
H
Kunisada
Takahiro
T
Yamashita
Satoshi
S
Mori
Hideki
H
D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051822:T Cell Transcription Factor 1 / Q000235:genetics*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051153:Wnt Proteins / Q000037:antagonists & inhibitors; D051176:beta Catenin / Q000235:genetics*
C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051822:T Cell Transcription Factor 1; D051153:Wnt Proteins; D051176:beta Catenin