Crosstalk between Integrin αvβ3 and Estrogen Receptor-α Is Involved in Thyroid Hormone-Induced Proliferation in Human Lung Carcinoma Cells

Meng, Ran; Tang, Heng Yuan; Westfall, Jennifer; London, David; Cao, James; Mousa, Shaker A.; Luidens, Mary K.; Hercbergs, Aleck; Davis, Faith B.; Davis, Paul J.; Lin, Hung-Yun

doi:10.1371/journal.pone.0027547

Cited by 87 publications

(82 citation statements)

References 37 publications

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“…Similar findings were observed in the EL4 cell line (data not shown). Additionally, other in vitro studies in human breast cancer lines (Tang et al 2004), papillary and follicular thyroid cells (Lin et al 2007), glioma U-87 MG cells (Lin et al 2009), and lung cancer cells (Meng et al 2011) showed that exposure to physiological concentrations of T 3 and T 4 induced cell proliferation through the activation of ERK1/2. Moreover, tumor-bearing hyperthyroid mice exhibited a decreased survival rate.…”

Section: Discussionmentioning

confidence: 96%

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Sterle¹,

Valli²,

Cayrol³

et al. 2014

Journal of Endocrinology

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We have shown in vitro that thyroid hormones (THs) regulate the balance between proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor development have been studied, but the results are still controversial. Herein, we show the modulatory action of thyroid status on the in vivo growth of T lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice received inoculations of EL4 cells to allow the development of solid tumors. Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced by the early appearance of palpable solid tumors and the increased tumor volume. These results are consistent with the rate of cell division determined by staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly from the euthyroid controls with respect to these parameters. Additionally, only tumors from hyperthyroid animals had increased expression levels of proliferating cell nuclear antigen and active caspase 3. Differential expression of cell cycle regulatory proteins was also observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL4 T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.

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Section: Discussionmentioning

confidence: 96%

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Sterle¹,

Valli²,

Cayrol³

et al. 2014

Journal of Endocrinology

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“…Tetrac has been shown to inhibit the short-term effects of thyroid hormone at the plasma membrane level (14,42) and is considered a probe for the involvement of the integrin ␣v␤3 in plasma membrane-initiated actions of T 4 ; the agent also exhibits pharmacological antitumor properties (19,26,44,49). As expected, tetrac (10 M) prevented the inhibitory effect of T 4 on IGF-I-induced glucose uptake; surprisingly, tetrac itself stimulated basal glucose uptake comparably to T 4 (Fig.…”

Section: Short-term Modulation By Thyroid Hormone Of Basal and Igf-i-mentioning

confidence: 99%

Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3

Incerpi

Hsieh

Lin

et al. 2014

American Journal of Physiology-Cell Physiology

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FB, Davis PJ. Thyroid hormone inhibition in L6 myoblasts of IGF-Imediated glucose uptake and proliferation: new roles for integrin ␣v␤3. Am J Physiol Cell Physiol 307: C150-C161, 2014. First published May 7, 2014 doi:10.1152/ajpcell.00308.2013.-Thyroid hormones L-thyroxine (T4) and 3,3=,5-triiodo-L-thyronine (T3) have been shown to initiate shortand long-term effects via a plasma membrane receptor site located on integrin ␣v␤3. Also insulin-like growth factor type I (IGF-I) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between T4 and IGF-I in rat L6 myoblasts, we have examined integrin ␣v␤3-mediated modulatory actions of T4 on glucose uptake, measured through carrier-mediated 2-deoxy-[3 H]-D-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [3 H]-thymidine incorporation, and fluorescence-activated cell sorting analysis. IGF-I stimulated glucose transport and cell proliferation via the cell surface IGF-I receptor (IGFIR) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free T4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4 were mediated by an Arg-GlyAsp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to ␣v␤3, and the T4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T4 of IGF-I-stimulated glucose uptake and cell proliferation. Western blotting confirmed roles for activated phosphatidylinositol 3-kinase and extracellular regulated kinase 1/2 (ERK1/2) in the effects of IGF-I and also showed a role for ERK1/2 in the actions of T4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts. glucose transport; insulin-like growth factor type I; fluorescenceactivated cell sorting; tetraiodothyroacetic acid; thyroxine; triiodothyronine; mitogen-activated protein kinase; extracellular regulated kinase 1/2; phosphatidylinositol 3-kinase

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“…Such reports are consistent with actions of T 4 initiated non-genomically at αvβ3 that support complex tumor cell proliferation and pro-angiogenic activities that downstream of the integrin depend upon gene transcription but do not involve TRs. L -thyroxine (T 4 ) is primarily cited in these cancer cell observations because, as pointed out above, the affinity of the hormone receptor on αvβ3 favors T 4 over T 3 [19], and studies of cancer cell proliferation have shown T 3 to be active only at supraphysiologic concentrations, whereas T 4 is active at physiologic free hormone levels [2,14].…”

Section: Possible Clinical Consequences Of the Overlap Of Genomic Andmentioning

confidence: 99%

Overlapping nongenomic and genomic actions of thyroid hormone and steroids

et al. 2011

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Crosstalk between Integrin αvβ3 and Estrogen Receptor-α Is Involved in Thyroid Hormone-Induced Proliferation in Human Lung Carcinoma Cells

Cited by 87 publications

References 37 publications

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3

Overlapping nongenomic and genomic actions of thyroid hormone and steroids

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