The participation of thiol-oxidoreductases such as thioredoxin during implantation, embryogenesis and fetal development has been extensively studied. Here, we analyzed the expression of the thioredoxin superfamily enzyme quiescin Q6/sulfhydryl oxidase (QSOX) during development. Results show that QSOX is present in fetal bovine serum (4 months' gestation), but its levels decrease with time after birth (from P1 to P60). We also demonstrate that a sulfhydryl oxidase activity correlates with QSOX expression in such sera, suggesting a putative role in the redox modulation of developmental programs.
High expression levels of hypoxia inducing factor 1 alpha are related to mammary carcinogenesis. In previous studies, we demonstrated that expression of transforming growth factor alpha increases upon treatment with triiodothyronine, but this expression does not occur in cellular models that do not express the estrogen receptor, or when cells are co-treated with the anti-estrogen, tamoxifen. The aim of this study was to determine the effect of the hormone triiodothyronine on the expression of the genes HIF1A and TGFA in the breast cancer cell line MCF7. The cell line was subjected to treatment with triiodothyronine at the supraphysiological dose of 10(-8)M for 10min, 30min, 1h, and 4h in the presence or absence of actinomycin D, the gene expression inhibitor, cycloheximide, the protein synthesis inhibitor, and LY294002, the phosphoinositide 3 kinase inhibitor. HIF1A and TGFA mRNA expression was analyzed by reverse transcription polymerase chain reaction. For data analysis, we used analysis of variance complemented by Tukey test and an adopted minimum of 5% significance. We found that HIF1A and TGFA expression increased in the presence of triiodothyronine at all times studied. HIF1A expression decreased in triiodothyronine-treated cells when gene transcription was also inhibited; however, TGFA expression decreased after 10 and 30min of treatment even when transcription was not inhibited. We found that activation of PI3K was necessary for triiodothyronine to modulate HIF1A and TGFA expression.
The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Thyroid hormone; Triiodothyronine; Breast cancer; Mammary gland and metabolism Core tip: Breast cancer (BC) is a malignant tumor occurring much more frequently in women than in men; worldwide, the incidence of BC has increased markedly in recent years. It is estimated that 1.7 million women will be diagnosed with BC in 2020, marking an increase of 26%, compared to the current incidence: 1.35 million new cases annually. Countless environmental risk factors, pathological conditions, and physiological agents, as well as thyroid hormones (THs), have been involved in the development of BC. Various lines of evidence suggest tumor-promoting effects of THs. The literature contains controversial reports regarding the relationship between thyroid diseases and BC; furthermore, studies reporting both an excess of and a lack of THs may affect breast development and progression to cancer. Epidemiologically, many studies suggest that hyperthyroidism is a factor in the development of BC. Furthermore, experimental studies have shown that high levels of THs reduce the interval of multiplication of BC cell lines. Therefore, the influence of THs on BC is unclear. However, the majority of BC research suggests a relationship, primarily, when the molecular aspects of these hormones are considered in the progression of this type of tumor.De Sibio MT, de Oliveira M, Moretto FCF, Olimpio RMC, Conde SJ, Luvizon AC, Nogueira CR. Triiodothyronine and breast TOPIC HIGHLIGHT Triiodothyronine and breast cancer INTRODUCTIONThyroid hormones (THs), 3,5,3′,-triiodothyronine (T3) and thyroxine (T4), play critical roles in the differentiation, growth, metabolism, and physiological function of nearly all mammalian tissues [1,2] ; in addition, they are required for amphibian metamorphosis [3] ....
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