Lee M L, Chen G G, Vlantis A C, Tse G M K, Leung B C H, van Hasselt C A
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China.
Cancer J. 2005 Mar-Apr;11(2):113-21. doi: 10.1097/00130404-200503000-00006.
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.
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.
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.
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.
甲状腺癌的特征之一是相对于男性，其更易发生于育龄女性。有文献记载，因妇科原因使用雌激素的女性患甲状腺癌的风险也会增加。本研究的目的是探讨目前尚不清楚的性激素促进甲状腺癌发生发展的机制。
在本研究中，我们通过MTT法研究了雌二醇和睾酮对人甲状腺乳头状癌细胞系（KAT5）细胞增殖的影响。我们还通过蛋白质免疫印迹法和逆转录聚合酶链反应分析研究了细胞中雌激素受体的表达以及抗凋亡蛋白Bcl-xL、促凋亡蛋白Bax的水平和信使核糖核酸。
结果显示，与用睾酮处理的细胞和未处理的细胞相比，雌二醇促进细胞增殖，并且他莫昔芬减弱了雌二醇的促生长作用。Bcl-xL的表达以剂量依赖性方式显著增加，导致Bcl-xL与Bax的比值升高。
我们得出结论，雌二醇促进KAT5细胞增殖，其潜在机制可能与Bcl-xL表达上调有关。这些数据为流行病学数据背后的分子机制提供了见解，该数据显示女性甲状腺癌的患病率比男性高两到三倍。从治疗角度来看，雌二醇增强抗凋亡信号通路这一发现可能对寻找甲状腺癌的新型预防和治疗策略具有重要意义。
