Chen, George G.1
, Wang, Sangsang1
, Ho, Jessica W.M.1
, Vlantis, Alexander C.1
, Liu, Shirley YW1
, Ng, Enders K.W.1
, Ng, Siu Kwan1
, Van Hasselt, Andrew C.1
, Tong, Michael C.F.1
1 Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China
Increasing evidence indicates a role of peroxisome proliferator-activated receptor gamma (PPAR?) in the proliferation and growth of papillary thyroid cancer (PTC). PPAR? usually needs to be activated by its ligands before it exerts the inhibitory effect on tumor cells. The objective of this study was to examine the status of endogenous ligands that has not been investigated in thyroid cancer.
We isolated the lysates of PTC tumor tissues and then measure the levels of 3 main endogenous ligands, 15-deoxy-?(12,14)-prostaglandin J2 (15d-PGJ2), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) using ELISA method. We also attempted to alter the levels of these ligands to check whether they would affect the survival/death of PTC cells.
The levels of these 3 endogenous ligands, 15(S)-HETE in particularly, were significantly reduced in tumor tissues of PTC compared with non-tumor thyroid tissues (p<0.01). In the cultured PTC cells (K1 and BCPAP), we found that the levels of these 3 ligands could be obviously increased by inhibiting estrogen receptor alpha (ERa) or activating estrogen receptor beta (ERb). Accompanied the upregulation of these ligands, the survival of PTC cells was reduced but the apoptosis was enhanced.
Discussion & Conclusion:
We have demonstrated that PTC is associated with reduced levels of endogenous PPAR? ligands and that the upregulation of the endogenous ligands, which are generally believed to be well tolerated and nontoxic, can promote the death of PTC cells.