PPARγ insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-κB signaling pathway

Publisher Website
Google Scholar
Abstract
The molecular genetic events underlying thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant thyroid hormone receptor (TRPV/PV mouse) spontaneously develop follicular thyroid carcinoma similar to human thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor (PPAR) could function as a tumor suppressor in thyroid cancer in vivo. Using the offspring from the cross of TRPV/+ and PPAR+/- mice, we found that thyroid carcinogenesis progressed significantly faster in TRPV/PV mice with PPAR insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPAR protein abundance led to the activation of the nuclear factor-B signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TRPV/PV mice with a PPAR agonist, rosiglitazone, delayed the progression of thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPAR is a critical modifier in thyroid carcinogenesis and could be tested as a therapeutic target in thyroid follicular carcinoma.

This publication has 46 references indexed in Scilit: