Conde Sandro José, Luvizotto Renata de Azevedo Melo, de Síbio Maria Teresa, Nogueira Célia Regina
Department of Biological Science, São Paulo Federal Institute (IFSP), 18136-540 São Roque, SP, Brazil ; Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil.
Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil.
ISRN Endocrinol. 2014 Feb 20;2014:317398. doi: 10.1155/2014/317398. eCollection 2014.
We investigated thyroid hormone levels in menopausal BrC patients and verified the action of triiodothyronine on genes regulated by estrogen and by triiodothyronine itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum TPO-AB, TSH, FT4, and estradiol, before and after surgery, and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, triiodothyronine, triiodothyronine plus 4-hydroxytamoxifen, 4-hydroxytamoxifen, estrogen, or estrogen plus 4-hydroxytamoxifen. Genes regulated by estrogen (TGFA, TGFB1, and PGR) and by triiodothyronine (TNFRSF9, BMP-6, and THRA) in vitro were evaluated. TSH levels in BrC patients did not differ from those of the control group (1.34 ± 0.60 versus 2.41 ± 1.10 μ U/mL), but FT4 levels of BrC patients were statistically higher than controls (1.78 ± 0.20 versus 0.95 ± 0.16 ng/dL). TGFA was upregulated and downregulated after estrogen and triiodothyronine treatment, respectively. Triiodothyronine increased PGR expression; however 4-hydroxytamoxifen did not block triiodothyronine action on PGR expression. 4-Hydroxytamoxifen, alone or associated with triiodothyronine, modulated gene expression of TNFRSF9, BMP-6, and THRA, similar to triiodothyronine treatment. Thus, our work highlights the importance of thyroid hormone status evaluation and its ability to interfere with estrogen target gene expression in BrC samples in menopausal women.
我们研究了绝经后乳腺癌（BrC）患者的甲状腺激素水平，并验证了三碘甲状腺原氨酸对雌激素调节基因以及三碘甲状腺原氨酸自身在BrC组织中调节基因的作用。我们选取了15名绝经后BrC患者以及18名无BrC的绝经后女性作为对照组。我们在手术前后测量了血清甲状腺过氧化物酶抗体（TPO-AB）、促甲状腺激素（TSH）、游离甲状腺素（FT4）和雌二醇，并采用免疫组织化学方法检测雌激素和孕激素受体。BrC原代组织培养物接受以下处理：乙醇、三碘甲状腺原氨酸、三碘甲状腺原氨酸加4-羟基他莫昔芬、4-羟基他莫昔芬、雌激素或雌激素加4-羟基他莫昔芬。评估了体外雌激素（TGFA、TGFB1和PGR）和三碘甲状腺原氨酸（TNFRSF9、BMP-6和THRA）调节的基因。BrC患者的TSH水平与对照组无差异（1.34±0.60对2.41±1.10μU/mL），但BrC患者的FT4水平在统计学上高于对照组（1.78±0.20对0.95±0.16ng/dL）。雌激素和三碘甲状腺原氨酸处理后，TGFA分别上调和下调。三碘甲状腺原氨酸增加了PGR表达；然而，4-羟基他莫昔芬并未阻断三碘甲状腺原氨酸对PGR表达的作用。单独或与三碘甲状腺原氨酸联合使用时，4-羟基他莫昔芬调节了TNFRSF9、BMP-6和THRA的基因表达，类似于三碘甲状腺原氨酸处理。因此，我们的研究突出了甲状腺激素状态评估的重要性及其干扰绝经后女性BrC样本中雌激素靶基因表达的能力。
