The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer cells
R Chu, C van Hasselt & G Chen
Both of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) contribute to the development of thyroid cancer. Previously, the activation of ERα was found to promote the proliferation of thyroid cancer cells, whereas activation of either ERβ or PPARγ resulted in apoptosis of thyroid cancer cells. Furthermore, a transactivation between ER and PPARγ was reported in estrogen-responsive malignancy, such as breast cancer. However, the relationship between ER and PPARγ in thyroid cancer remains unknown. In this study, we used thyroid papillary carcinoma cells (K1) and anaplastic carcinoma cells (FRO) to examine the interaction between ER and PPARγ. We found that PPARγ protein expression and activity was reduced by over-expression of either ERα or ERβ. PPARγ agonist rosiglitazone (RTZ) could overcome the effects of ERα or ERβ over-expression on PPARγ. The application of RTZ also reduced the expression of ERα and ERβ proteins. Furthermore, knockdown of PPARγ increased ERα and ERβ expression, as well as ER activity. The results of MTT and wound healing assays showed that increment of ERα and ERβ had opposite effects on cell proliferation and migration. While the enhancement of PPARγ by RTZ lessened the proliferative effect of ERα but raised the inhibitory impact of ERβ, especially in K1 cells. Finally, the interaction between ER and PPARγ altered levels of cytoplasmic fractions of apoptosis-inducing factor (AIF), cytochrome c (cyto c), caspase 3 and mitochondrial Bax, indicating involvement of the non-genomic apoptosis pathway. Collectively, these findings provide evidence of cross-talk between ER and PPARγ and a cooperatively inhibitory function of ERβ and PPARγ in thyroid cell proliferation and migration. These findings support the cross-talk between ER and PPARγ contributes to thyroid carcinogenesis and they may provide some clues for the development of novel therapeutic strategy against thyroid cancer.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Figure 1 ERa , ER b and PPAR, expressions in thyroid cell lines.