Growth inhibitory effects of thyroid hormones on androgen-dependent mammary tumor cells (original) (raw)
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Effect of thyroid hormones on androgen responsiveness in a mammary tumor cell line
Journal of steroid biochemistry, 1981
Androgen sensitive cells derived from the androgen responsive Shionogi 115 mouse mammary carcinoma. when cultured for 4 weeks in testosterone free medium lose their androgen responsiveness. Thyroid hormones influence this loss of steroid sensitivity especially if cells are cultured in medium supplemented with serum treated with ACiI x IO resin which specifically removes thyroid hormones from it. These hormones slow down the loss of androgen responsiveness, maintaining the cells more responsive to the stimulatory effect of testosterone. without producing any detectable change in androgen receptor c&tent. As the transition to androgen unresponsive status is accompanied in S 115 cells by profound changes in cell morphology, it is reasonable to hypothesize that thyroid hormones exert their effect through modifications of cell membrane properties.
Influence of thyroid hormone receptors on breast cancer cell proliferation
Annals of Oncology, 2005
Background: The involvement of thyroid hormones in the development and differentiation of normal breast tissue has been established. However, the association between breast cancer and these hormones is controversial. Therefore, the objective of the present study was to determine the protein expression pattern of thyroid hormone receptors in different human breast pathologies and to evaluate their possible relationship with cellular proliferation.
Cancer Research
DNA synthesis of SC-3 cells cloned from mouse mammary carcinoma (Shionogi carcinoma 115) was remarkably enhanced by androgen as well as basic fibroblast growth factor (bFGF) at the early phase (days 1-3) of stimulation in serum-free culture condition. However, bFGF-induced DNA synthesis could not be observed at the late phase (days 4-6) of stimulation while androgen was able to continuously elicit DNA synthesis. When the effect of androgen on cell yield was examined, the cell number was increased while bFGF could not enhance cell growth. Androgen-induced heparin-binding growth factor partially purified from conditioned medium behaved like bFGF in terms of DNA synthesis and replication in SC-3 cells. SC-3 cells were found to contain the high-affinity binding site toward triiodothyronine. The dissociation constant and the maximum number of the binding sites were 7 x 10(-10) M and 1800/cell, respectively. Triiodothyronine significantly blunted the testosterone-induced DNA synthesis. On...
Estrogen Promotes Growth of Human Thyroid Tumor Cells by Different Molecular Mechanisms 1
The Journal of Clinical Endocrinology & Metabolism, 2001
Thyroid tumors are about 3 times more frequent in females than in males. Epidemiological studies suggest that the use of estrogens may contribute to the pathogenesis of thyroid tumors. In a very recent study a direct growth stimulatory effect of 17-estradiol was demonstrated in FRTL-5 rat thyroid cells. In this work the presence of estrogen receptors ␣ and  in thyroid cells derived from human goiter nodules and in human thyroid carcinoma cell line HTC-TSHr was demonstrated. There was no difference between the expression levels of estrogen receptor ␣ in males and females, but there was a significant increase in expression levels in response to 17-estradiol. Stimulation of benign and malignant thyroid cells with 17-estradiol resulted in an increased proliferation rate and an enhanced expression of cyclin D1 protein, which plays a key role in the regulation of G 1 /S transition in the cell cycle. In malignant tumor cells maximal cyclin D1 expression was observed after 3 h, whereas in benign cells the effect of 17-estradiol was delayed. ICI 182780, a pure estrogen antagonist, prevented the effects of 17-estradiol. In addition, 17estradiol was found to modulate activation of mitogen-activated protein (MAP) kinase, whose activity is mainly regulated by growth factors in thyroid carcinoma cells. In response to 17-estradiol, both MAP kinase isozymes, extracellular signal-regulated protein kinases 1 and 2, were strongly phosphorylated in benign and malignant thyroid cells. Treatment of the cells with 17-estradiol and MAP kinase kinase 1 inhibitor, PD 098059, prevented the accumulation of cyclin D1 and estrogen-mediated mitogenesis. Our data indicate that 17estradiol is a potent mitogen for benign and malignant thyroid tumor cells and that it exerts a growth-promoting effect not only by binding to nuclear estrogen receptors, but also by activation of the MAP kinase pathway.
Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms
Journal of Clinical …, 2001
Thyroid tumors are about 3 times more frequent in females than in males. Epidemiological studies suggest that the use of estrogens may contribute to the pathogenesis of thyroid tumors. In a very recent study a direct growth stimulatory effect of 17-estradiol was demonstrated in FRTL-5 rat thyroid cells. In this work the presence of estrogen receptors ␣ and  in thyroid cells derived from human goiter nodules and in human thyroid carcinoma cell line HTC-TSHr was demonstrated. There was no difference between the expression levels of estrogen receptor ␣ in males and females, but there was a significant increase in expression levels in response to 17-estradiol. Stimulation of benign and malignant thyroid cells with 17-estradiol resulted in an increased proliferation rate and an enhanced expression of cyclin D1 protein, which plays a key role in the regulation of G 1 /S transition in the cell cycle. In malignant tumor cells maximal cyclin D1 expression was observed after 3 h, whereas in benign cells the effect of 17-estradiol was delayed. ICI 182780, a pure estrogen antagonist, prevented the effects of 17-estradiol. In addition, 17estradiol was found to modulate activation of mitogen-activated protein (MAP) kinase, whose activity is mainly regulated by growth factors in thyroid carcinoma cells. In response to 17-estradiol, both MAP kinase isozymes, extracellular signal-regulated protein kinases 1 and 2, were strongly phosphorylated in benign and malignant thyroid cells. Treatment of the cells with 17-estradiol and MAP kinase kinase 1 inhibitor, PD 098059, prevented the accumulation of cyclin D1 and estrogen-mediated mitogenesis. Our data indicate that 17estradiol is a potent mitogen for benign and malignant thyroid tumor cells and that it exerts a growth-promoting effect not only by binding to nuclear estrogen receptors, but also by activation of the MAP kinase pathway.
Experientia, 1975
complement. Further, the cells consistantly fail to provoke tumors in appropriate hosts, and have been maintained for up to 20 months and 27 pasages in culture. These normal characteristics have been retained despite the fact that the only difference in treatment of these control cells from that of the transformed cells was the presence or absence of benzo(a)pyrene. DIPAOLO et al. 8,9 performed chromosomal analyses of chemically transformed hamster and rat cultures and of tumors induced by these ceils. They found that the cells were, generally, near-diploid. Analysis of our transformed cultures show chromosomal anomalies in 83% of the dividing cells, including 5 different types of aberrations. We are currently engaged in chromosomal analysis of other transformed hamster cell lines to determine if these aberrations are specific for B(a)P induced transformation or are common to other transformations in culture.
Triiodothyronine and breast cancer
World Journal of Clinical Oncology, 2014
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.
Endocrine Pathology, 2001
Differential effects of testosterone and estradiol on the proliferation of human thyroid papillary (NPA-87-1) and follicular (WRO-82-1) carcinoma cell lines were assessed by [ 3 H]-thymidine incorporation and the cell number. Cells (2.5 × 10 5) plated in 24-well culture plates in 400 µL RPMI-1640 medium/well, under 5% CO 2 and 95% air, at 37°C were exposed to linearly increasing concentrations of human thyroid-stimulating hormone (hTSH) (1.25-640 ng/mL), testosterone (1.25-640 ng/mL), or estradiol (1.25-640 pg/mL) for 24 h. Testosterone and estradiol increased the proliferation of NPA cell line in a dosedependent manner; flutamide (an anti-androgen) and tamoxifen (an anti-estrogen) (10-8 , 10-7 , 10-6 , and 10-5 mol/L) effectively inhibited the testosterone and estradiol-induced cell proliferation, respectively. While flutamide inhibited the stimulatory effect of testosterone on the WRO cell line, tamoxifen augmented the inhibitory effect of estradiol. TSH did not have any effect on the proliferation of NPA or WRO cell lines, and testosterone-estradiol had no impact on TSH binding to these cells. N-ethylmalemide (5α-reductase inhibitor) (10-8-10-5 mol/L) did not modulate basal and testosterone-induced cell proliferation, indicating the direct effect of testosterone without getting converted into dihydrotestosterone (DHT). Both the cell lines tested positive for androgen and estrogen receptors and were up-regulated by the respective ligands. It is concluded that testosterone and estradiol modify the proliferation of thyroid cancer cells through homologous up-regulation of their own receptors, which is independent of TSH, and their effects may vary according to the cell type.
Altered response to thyroid hormones by prostate and breast cancer cells
Cancer Chemotherapy and Pharmacology, 2000
Transferrin, an abundant bone marrow constituent, has been shown to be a potent mitogen in vitro in the prostate cancer cell line PC3. T4 (L-thyroxine) and T3 (3¢,3,5-tri-iodo-L-thyronine) are regulators of cell metabolism. In this study, the eects of nonphysiological concentrations (about two orders of magnitude higher) of T4, T3, T2 (3,5-di-iodo-L-thyronine), RT3 (reverse T3, 3¢,5¢,3-tri-iodo-L-thyronine) and transferrin (about three orders of magnitude lower) were tested on the prostate cancer cell lines PC3, DU145 and LNCaP, and the breast cancer cell line MCF-7. In PC3 cells, increased proliferation by transferrin could be reversed by the addition of T3 or T4. T4 decreased proliferation in all cell lines tested, while transferrin increased proliferation in PC3 cells only. T3 decreased proliferation in PC3, LNCaP and MCF-7 cells but had no eect on DU145 cells. T4 and T3 gave two-state behavior in LNCaP cells. These results were combined to determine the essential iodines which produced the observed proliferative eects. Cell lines responded dierently to T4, T3, T2, RT3 and transferrin suggesting a speci®c interaction among the compounds tested and the dierent cell lines. Finally, regulation of gene expression was demonstrated using DU145 cells. Upregulation of c-fos mRNA was observed in cultures at early time-points in the presence of T4, transferrin or both. Decreased expression was observed at later time-points with no expression at 4 h. An explanation for these results may be a change in thyroid hormone receptor/ligand anity. Thus, the interactions between thyroid hormones and cancer cells may be dierent from those between thyroid hormones and normal cells.