Oestrogen mediates the growth of human thyroid carcinoma cells via an oestrogen receptor-ERK pathway.
OBJECTIVE
Although thyroid cancer occurs much more frequently in females, the role of sex hormones in thyroid carcinogenesis is unknown. In this study, it has been investigated how 17beta-oestradiol (E2) influenced proliferation and growth of thyroid cancer cells.


METHODS
Cell proliferation and its related molecules were examined in thyroid papillary carcinoma cells (KAT5), follicular thyroid carcinoma cells (FRO) and anaplastic carcinoma cells (ARO). Levels of oestrogen receptor (ER) alpha and beta were regulated by their agonists (PPT and DPN), antagonists and siRNA.


RESULTS
E2 promoted cell proliferation. Such an effect was positively related to ERalpha but negatively to ERbeta; PPT enhanced cell proliferation while DPN inhibited it. PPT increased Bcl-2 expression while DPN decreased it. DPN also elevated Bax expression. PPT elevated the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), suggesting a positive role of ERK1/2 in E2-induced cell proliferation. Knockdown of ERalpha significantly attenuated E2-mediated Bcl-2 and pERK1/2 expression. In contrast, knockdown of ERbeta markedly enhanced them.


CONCLUSIONS
Oestrogen stimulates proliferation of thyroid cancer cells, associated with increase in Bcl-2 and decrease in Bax levels in an ERK1/2-related pathway. Imbalance between ERalpha and ERbeta may contribute to thyroid carcinogenesis.
Zeng
Q
Q
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
Chen
G G
GG
Vlantis
A C
AC
van Hasselt
C A
CA
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D010766:Phosphorylation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3