Thyroid hormone and anti-apoptosis in tumor cells

Lin, Hung Yun; Glinsky, Gennadi; Mousa, Shaker A.; Davis, Paul J.

doi:10.18632/oncotarget.4023

Cited by 55 publications

(44 citation statements)

References 75 publications

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“…In the present work, the thyroid hormones inhibited in A2780 cells the expression of FAS (CD95), a cell surface death‐receptor that is known for its ability to mediate apoptosis . Similar suppression of FAS in other cell models was previously shown by T3 and T4, supporting the anti‐apoptotic action of thyroid hormones in cancer. However, in OVCAR‐3 cells, in which an anti‐apoptotic effect by the hormones was previously reported, an induction in FAS expression was documented.…”

Section: Discussionsupporting

confidence: 88%

“…13 In the majority of the genes examined in the current work, the effects of T3 In the present work, the thyroid hormones inhibited in A2780 cells the expression of FAS (CD95), a cell surface death-receptor that is known for its ability to mediate apoptosis. 23 Similar suppression of FAS in other cell models was previously shown by T3 and T4, 45,48,50 supporting the anti-apoptotic action of thyroid hormones in cancer.…”

Section: Discussionsupporting

confidence: 71%

“…Moreover, T3 has been shown before, in another tumor model, to inhibit IGFBP‐6 expression . Lastly, regarding Apaf1 , NOXA , BAX , Caspase ‐3, and FAS , an association between transcriptional control by thyroid hormones was suggested in other tumor models . Regarding polR2A , ERCC5 , ZMAT‐3 , and Bnip3 , to the best of our knowledge, our work is the first to report an association between the expression of these genes and thyroid hormones.…”

Section: Discussionsupporting

confidence: 66%

“…44 Lastly, regarding Apaf1, NOXA, BAX, Caspase-3, and FAS, an association between transcriptional control by thyroid hormones was suggested in other tumor models. 4,6,[45][46][47][48] Regarding polR2A, ERCC5, ZMAT-3, and…”

Section: Discussionmentioning

confidence: 99%

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Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

Shinderman-Maman

Weingarten

Moskovich

et al. 2017

Molecular Carcinogenesis

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The regulation of cancer-relevant genes by the thyroid hormones, 3, 5, 3′-Triiodo-Lthyronine (T3) and L-thyroxine (T4), was recently acknowledged. However, limited data exists on the hormonal effects on gene expression in ovarian cancer, a gynecological malignancy associated with a low cure rate. The expression of fifteen genes involved in DNA repair, cell cycle, apoptosis, and tumor suppression was evaluated in OVCAR-3 and A2780 cell lines, using real-time PCR following short incubation with T3 (1 nM) or T4 (100 nM). The thyroid hormones downregulated the expression of the majority of genes examined. Support for the involvement of the MAPK and PI3K in thyroid hormone-mediated gene expression was shown for a set of genes. FAS expression was inhibited in A2780 cells, while an unexpected induction was demonstrated in OVCAR-3 cells. An analogous effect on the protein levels of FAS receptor and its soluble form was demonstrated by Western blotting. We further established, using primer sets that discriminate between the different RNA isoforms, that the hormones increase the mRNA levels of both coding and non-coding FAS mRNAs. The prevalence of these isoforms, using The Cancer Genome Atlas (TCGA) analysis, was significantly more abundant in 17 cancer types, including ovarian cancer, compared to normal tissues. Our results highlight the role of thyroid hormones in the expression of cancer-relevant-genes in ovarian cancer and provide an important insight into the pathways by which mitogenic and anti-apoptotic effects are exerted. This integrin contains an Arg-Gly-Asp (RGD) recognition site that binds extra cellular matrix (ECM) proteins containing this sequence. At close proximity to the RGD recognition site, a thyroid hormone receptor was described. 1,2 The receptor is complex and includes a site for T3 and a second site for T3 and for L-thyroxine (T4), 3 the principal secretory product of the thyroid gland. Physiological levels of T4 activate the thyroid hormone receptor on αvβ3, whereas supraphysiologic concentrations of T3 are required to achieve stimulation at this Molecular Carcinogenesis. 2018;57:97-105.wileyonlinelibrary.com/journal/mc

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

Shinderman-Maman

Weingarten

Moskovich

et al. 2017

Molecular Carcinogenesis

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“…Tetraiodothyroacetic acid (tetrac) is a deaminated analog of T 4 that competes with thyroid hormone for a target or receptor on cell surface integrin α v β 3 and blocks the activity of thyroid hormone at this site . In addition to blocking the binding of thyroid hormone to integrin α v β 3 , tetrac and its nanoparticulate derivative nano‐diamino‐tetrac inhibit cancer cell proliferation and angiogenesis by disordering the expression of a number of genes relevant to apoptosis and blood vessel formation.…”

Section: The Interactions Between Steroid Hormones and Resveratrolmentioning

confidence: 99%

Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

Lin

Hsieh

Cheng

et al. 2017

Annals of the New York Academy of Sciences

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Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin α β for nonpeptide hormones. Interaction between hormones and integrin α β can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin α β . Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin α β blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. .

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Nongenomic Actions of Thyroid Hormones

Incerpi¹,

Davis²,

Pedersen³

et al. 2016

Endocrinology

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Nongenomic actions of thyroid hormone do not require a direct interaction of 3,5,3 0-triiodo-L-thyronine (T 3) with the transcriptionally active nuclear receptors TRα and TRβ. A rapid response time is a characteristic of many nongenomic actions; the onset of the majority of these effects is within minutes because the action is independent of gene expression and protein synthesis. While only T 3 is able to generate a genomic response, the different nongenomic effects may be activated by either T 3 or T 4 or by other iodothyronine derivatives such as T 2. In the last decade, the discovery of a large number of nongenomic actions of thyroid hormones has increasingly attracted the interest of researchers, and different specific binding sites or receptors for these hormones/messengers have now been described in several cellular compartments, including the external surface of the plasma membrane. The function of nongenomic effects of these hormones has mainly been considered to relate to homeostasis, such as actions on plasma membrane ion transporters or maintenance of the cytoskeleton, but recent evidence supports the existence of crosstalk between nongenomic and genomic effects of the hormone. Further examination of such crosstalk may reveal hitherto unappreciated mechanisms underlying global illnesses, such as cardiovascular diseases, inflammatory and immune diseases, and mechanisms of tumor cell function. Indeed, these new aspects have already improved our understanding of the contributions of nongenomic thyroid hormone actions to the regulation of cancer-related angiogenesis and to cancer cell survival pathways. In the present report, we provide a concise overview of the main observations that define the nongenomic actions of thyroid hormones and give a description of the state of the art.

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Thyroid hormone and anti-apoptosis in tumor cells

Cited by 55 publications

References 75 publications

Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

Nongenomic Actions of Thyroid Hormones

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