Induction of thyroid papillary carcinoma cell proliferation by estrogen is associated with an altered expression of Bcl-xL.
OBJECTIVE
One of the features of thyroid carcinoma is its predilection for women of reproductive age relative to men. An increased risk has also been documented in women who have used estrogens for gynecologic reasons. The aim of this study was to explore the mechanism by which sex hormones contribute to the development of thyroid carcinoma, which is not well understood at present.


METHODS
In this study, we investigated the effects of estradiol and testosterone on cell proliferation in a human thyroid papillary carcinoma cell line (KAT5) by MTT assay. We also studied the expression of estrogen receptors and the levels of anti-apoptotic Bcl-xL protein, pro-apoptotic Bax protein, and messenger RNA in the cells by Western blot and reverse transcriptase polymerase chain reaction analysis.


RESULTS
The results showed that estradiol promotes cell proliferation when compared with cells treated with testosterone and untreated cells, and that the growth-promoting effect of estradiol was attenuated by tamoxifen. The expression of Bcl-xL was markedly increased in a dose-dependent manner, resulting in an elevated ratio of Bcl-xL to Bax.


CONCLUSIONS
We conclude that estradiol promotes KAT5 cell proliferation and that the underlying mechanism may be associated with up-regulation of Bcl-xL expression. The data provide insight into the molecular mechanism underlying the epidemiologic data that shows a two- to threefold increased prevalence of thyroid carcinoma in women relative to men. From the therapeutic point of view, the finding that estradiol enhances anti-apoptotic signaling pathways may be significant in the search for novel prevention and treatment strategies of thyroid carcinomas.
Lee
M L
ML
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China.
Chen
G G
GG
Vlantis
A C
AC
Tse
G M K
GM
Leung
B C H
BC
van Hasselt
C A
CA
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D014481:United States / Q000453:epidemiology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D051020:bcl-X Protein; D013739:Testosterone