The effects of ionizing radiation on the activation of [beta]-catenin and Tcf-dependent signaling.
Published: 2005
Language: eng
Number of pages: 82
Description: Radiotherapy is associated with a risk of skin complications, including fibrosis and deficient wound healing. Beta-catenin mediated Tcf-dependent transcription is transiently activated in fibroblasts during the proliferative phase of wound healing. Surprisingly, 5Gy ionizing radiation increased beta-catenin protein levels, and it's transcriptional activity in fibroblasts. In the presence of Mg132, beta-catenin protein levels increased following irradiation suggesting a proteasomal independent mechanism. However, in the presence cycloheximide, beta-catenin protein levels did not increase following irradiation suggesting a translational dependent mechanism. Following irradiation phopho-Ser9-GSK3-beta protein levels increased, and in the presence of Dkk1, there was no elevation in beta-catenin protein, suggesting activation through the canonical wnt signaling pathway. Furthermore, irradiated beta-catenin stabilized primary fibroblasts had greater number of cells entering S-phase. Since hyperactivity of beta-catenin mediated Tcf-dependent transcription can cause hypertrophic wounds, it is possible that the increase in beta-catenin with irradiation is partly responsible for the phenomenon of radiation induced fibrosis.
Notes: Source: Masters Abstracts International, Volume: 44-02, page: 0762.

Thesis (M.Sc.)--University of Toronto, 2005.

Electronic version licensed for access by U. of T. users.

GERSTEIN MICROTEXT copy on microfiche (1 microfiche).