title: Further upregulation of beta-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of ApcMin/+ mice.
abstract: 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.
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Oyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirata
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Sheng
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
mesh_terms: 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*
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051822:T Cell Transcription Factor 1; D051153:Wnt Proteins; D051176:beta Catenin