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Thyroid hormone status interferes with estrogen target gene expression in breast cancer samples of menopausal women
Author(s) -
Conde Sandro José,
Luvizotto Renata de Azevedo M.,
Síbio Maria Teresa,
Nogueira Célia Regina
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.609.3
Subject(s) - medicine , tamoxifen , endocrinology , thyroid , estrogen , triiodothyronine , breast cancer , thyroid peroxidase , hormone , cancer
We investigated thyroid hormone levels in menopausal BrC patients, and verified the action of triiodothyronine (T3) on genes regulated by estrogen (E2) and by T3 itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum thyroid peroxidase antibody, TSH, free thyroxine, and estradiol, before and after surgery, and used immunohistochemistry to examine E2 and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, T3, T3+tamoxifen (TAM), TAM, E2, or E2+TAM. Genes regulated by E2 (TGFA, TGFB1, PGR) and by T3 (TNFRSF9, BMP‐6, THRA) in vitro were evaluated in each patient. Three BrC patients presented with clinical hyperthyroidism. Thyroxine levels of BrC patients were statistically higher than controls (1.78±0.20 vs. 0.95±0.16 ng/dl). TGFA and TGFB1 were upregulated and downregulated, respectively, after E2 and T3 treatment. T3 treatment increased PGR expression, however TAM did not block T3 action on PGR expression. TAM, alone or associated with T3, modulated gene expression of TNFRSF9, BMP‐6 and THRA, similar to T3 treatment, showing that TAM can interfere with gene expression modulated by T3. Our results reinforce that the thyroid hormone status of BrC patients can influence E2‐controlled processes, even after TAM intervention and/or in the absence of circulating E2 postmenopause.