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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer
Ryan Chu1, Andrew van Hasselt, Alexander C Vlantis
1Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong, China.
Background:
Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied.
Methods:
The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERβ agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis.
Results:
PPARγ protein and activity were reduced by the over-expression of either ERα or ERβ, whereas repression of ERα or ERβ increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERβ activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERβ and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor.
Conclusions:
This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERβ significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.
Insights
This study reveals a novel interaction between estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) in thyroid cancer. Their cross-talk, particularly involving ERβ and PPARγ, inhibits cancer cell growth and migration, offering new therapeutic avenues.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are implicated in thyroid cancer development and treatment.
- The interaction between ER and PPARγ in thyroid tumorigenesis remains unexplored.
Purpose of the Study:
- To investigate the interplay between ER (ERα and ERβ) and PPARγ in thyroid cancer cells.
- To determine the functional consequences of this interaction on cancer cell behavior and apoptosis.
Main Methods:
- Examined the impact of ER modulation (over-expression/down-expression) on PPARγ activity in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells.
- Assessed the effects of PPARγ modulation on ER expression and activity.
- Evaluated cellular proliferation, migration, and apoptosis following these modulations.
Main Results:
- ER over-expression reduced PPARγ activity, while ER repression increased it. PPARγ knockdown enhanced ER expression.
- Rosiglitazone (RTZ) counteracted ER effects and reduced ER expression, especially in PTC cells.
- ERβ and PPARγ interaction promoted apoptosis by upregulating caspase-3 and apoptosis-inducing factor.
Conclusions:
- Demonstrated a significant cross-talk between ER and PPARγ in thyroid cancer.
- The reciprocal interaction between PPARγ and ERβ inhibits thyroid cancer cell proliferation and migration.
- This interaction presents a potential new therapeutic strategy for thyroid cancer treatment.
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