scholarly journals Association between the expression of E1A oncogene and increased sensitivity to growth inhibition induced by sustained levels of cAMP in rat thyroid cells

2000 ◽  
pp. 286-293 ◽  
Author(s):  
G Villone ◽  
G De Vita ◽  
P Chieffi ◽  
A Picascia ◽  
R Stanzione ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Latency Period ◽  
Polyoma Virus ◽  
Thyroid Cell ◽  
Intracellular Camp ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Camp Levels ◽  
In Cells

OBJECTIVE: The aim of this study was to investigate: (i) whether a persistent increase of cAMP interferes with the proliferation of transformed thyroid cells, and (ii) whether the degree of malignancy is correlated with the sensitivity to a transient and/or sustained increase in intracellular cAMP levels. DESIGN AND METHODS: To address these questions we used thyroid cell lines transformed with E1A oncogene from adenoviruses 5 (PC E1A cell line) or 2 (PC HE4 cell line), or infected with the polyoma murine leukemia virus (PC PyMLV cell line) carrying the middle T gene of the polyoma virus, or, finally, expressing both E1A and PyMLV. These cell lines present various degrees of malignancy: PC EIA and PC HE4 cells are not tumorigenic; PC PyMLV cells induce non-invasive tumors after a long latency period; and PC EIA+PyMLV cells are highly tumorigenic. RESULTS AND CONCLUSIONS: Thyroid cell proliferation required the transient increase of intracellular cAMP levels, while persistent elevation of cAMP blocked the proliferation of normal thyroid PC Cl 3 cells and of PC Cl 3 cells transformed by a variety of different oncogenes. In addition, sustained levels of cAMP induced apoptosis in cells carrying the adenovirus EIA oncogene, but not in cells transformed with other oncogenes or in the wild-type PC Cl 3 cells. Furthermore, middle T gene of the polyoma virus seemed to afford protection only from apoptosis induced by cAMP when middle T is present in thyroid cells along with the E1A gene.

scholarly journals Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1518
Author(s):  
Maria Qatato ◽  
Vaishnavi Venugopalan ◽  
Alaa Al-Hashimi ◽  
Maren Rehders ◽  
Aaron D. Valentine ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Lines ◽  
Human Thyroid ◽  
Apical Plasma Membrane ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Trace Amine ◽  
Rat Thyroid

Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation.

Adhesion molecule expression by the FRTL-5 rat thyroid cell line

1991 ◽  
Vol 130 (3) ◽  
pp. 451-456 ◽  
Author(s):  
N. Tandon ◽  
C. Dinsdale ◽  
T. Tamatani ◽  
M. Miyasaka ◽  
A. P. Weetman
Keyword(s):  
Cell Line ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Thyroid Cell ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Rat Thyroid

ABSTRACT We have examined the expression and function of rat CD54, a homologue of human intercellular adhesion molecule-1 (ICAM-1), by the continuously growing rat thyroid cell line FRTL-5. Approximately 10% of FRTL-5 cells express CD54 under basal conditions and this is not influenced by thyrotrophin. Expression of CD54 is increased by cytokines (γ-interferon, tumour necrosis factor, interleukin-1) and by an activator of C-kinase, phorbol 12-myristate 13-acetate. Blocking ICAM-1 with a monoclonal antibody directed against this molecule significantly (P <0·01) reduced the binding of splenic lymphocytes to FRTL-5 cells but inhibition was consistently greater (P <0·01) in the presence of antibodies against a rat homologue of lymphocyte function-associated antigen-1, the receptor on T cells for ICAM-1. In no case was complete blocking of cluster formation observed. These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis. Journal of Endocrinology (1991) 130, 451–456

scholarly journals Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells

1999 ◽  
pp. 94-103 ◽  
Author(s):  
T Kimura ◽  
JE Dumont ◽  
A Fusco ◽  
J Golstein
Keyword(s):  
Protein Synthesis ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Cell Lines ◽  
Insulin Action ◽  
Cell Mass ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Stimulation Of

In the rat thyroid cell lines PC Cl3, FRTL- 5 and WRT, proliferation is mainly regulated by insulin or IGF, and TSH. However, the mechanism regulating cell mass doubling prior to division is still unknown. Our laboratory has shown that in dog thyroid cells insulin promotes growth in size while TSH in the presence of insulin triggers DNA replication. In the absence of insulin, TSH has no effect on cell growth. In this report we investigated insulin action on both cell mass and DNA synthesis and its modulation by TSH and insulin in PC Cl3 and FRTL-5 cells. In PC Cl3 cells, insulin activated not only DNA synthesis but also protein synthesis and accumulation. Although TSH potentiated the stimulation of DNA synthesis induced by insulin, enhancement of protein synthesis by both agents was additive. All TSH effects were reproduced by forskolin. Similar effects were also obtained in FRTL-5 cells. This suggests that insulin and TSH, via cAMP, modulate both growth in size and DNA replication in these cell lines. Lovastatin, which blocks 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreased the induction of DNA synthesis, but not of protein synthesis induced by insulin or TSH in PC Cl3 cells. In FRTL-5 cells, lovastatin reduced protein and DNA synthesis stimulated by insulin but not TSH-induced protein synthesis. Taking these data together, we propose that insulin and/or TSH both modulate cell mass doubling and DNA synthesis in these cell lines, presumably via different pathways, and that there are at least two pathways which regulate growth in size in FRTL-5 thyroid cells: one triggered by insulin, which is lovastatin sensitive, and the other activated by TSH, which is not sensitive to lovastatin.

Differential effects of interleukin 1α and 1β on cultured human and rat thyroid epithelial cells

1990 ◽  
Vol 122 (4) ◽  
pp. 520-526 ◽  
Author(s):  
Å. Krogh Rasmussen ◽  
L. Kayser ◽  
K. Bech ◽  
U. Feldt-Rasmussen ◽  
H. Perrild ◽  
...  
Keyword(s):  
Cell Line ◽  
Interleukin 1 ◽  
Cell System ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Camp Production ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Interleukin 1Α ◽  
Rat Thyroid

Abstract The effects of human recombinant interleukin 1α (20 pg/1-2 μg/l) and 1β (200 pg/1-20 μg/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1β (20 ng/1-20 μg/l), but not by interleukin 1α. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

2014 ◽  
Vol 307 (12) ◽  
pp. C1102-C1112 ◽  
Author(s):  
L. Twyffels ◽  
A. Strickaert ◽  
M. Virreira ◽  
C. Massart ◽  
J. Van Sande ◽  
...  
Keyword(s):  
Cell Lines ◽  
Apical Membrane ◽  
Specific Inhibitor ◽  
Anion Channel ◽  
Thyroid Cell ◽  
Anoctamin 1 ◽  
Thyroid Cells ◽  
Rat Thyroid

Iodide is captured by thyrocytes through the Na+/I− symporter (NIS) before being released into the follicular lumen, where it is oxidized and incorporated into thyroglobulin for the production of thyroid hormones. Several reports point to pendrin as a candidate protein for iodide export from thyroid cells into the follicular lumen. Here, we show that a recently discovered Ca2+-activated anion channel, TMEM16A or anoctamin-1 (ANO1), also exports iodide from rat thyroid cell lines and from HEK 293T cells expressing human NIS and ANO1. The Ano1 mRNA is expressed in PCCl3 and FRTL-5 rat thyroid cell lines, and this expression is stimulated by thyrotropin (TSH) in rat in vivo, leading to the accumulation of the ANO1 protein at the apical membrane of thyroid follicles. Moreover, ANO1 properties, i.e., activation by intracellular calcium (i.e., by ionomycin or by ATP), low but positive affinity for pertechnetate, and nonrequirement for chloride, better fit with the iodide release characteristics of PCCl3 and FRTL-5 rat thyroid cell lines than the dissimilar properties of pendrin. Most importantly, iodide release by PCCl3 and FRTL-5 cells is efficiently blocked by T16Ainh-A01, an ANO1-specific inhibitor, and upon ANO1 knockdown by RNA interference. Finally, we show that the T16Ainh-A01 inhibitor efficiently blocks ATP-induced iodide efflux from in vitro-cultured human thyrocytes. In conclusion, our data strongly suggest that ANO1 is responsible for most of the iodide efflux across the apical membrane of thyroid cells.

scholarly journals AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 785 ◽  
Author(s):  
Francesca Collina ◽  
Lucia La Sala ◽  
Federica Liotti ◽  
Nella Prevete ◽  
Elvira La Mantia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Braf V600e ◽  
Specific Gene ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Viral Oncogene ◽  
Rat Thyroid ◽  
Viral Oncogene Homolog

Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.

scholarly journals EGF and TGF-1 Effects on Thyroid Function

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Gabriella Mincione ◽  
Maria Carmela Di Marcantonio ◽  
Chiara Tarantelli ◽  
Sonia D'Inzeo ◽  
Arianna Nicolussi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Cross Talk ◽  
Early Stage ◽  
Tumor Promoter ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Tumors ◽  
Thyroid Cells ◽  
Rat Thyroid

Normal epithelial thyroid cells in culture are inhibited by TGF-1. Instead, transformed thyroid cell lines are frequently resistant to its growth inhibitory effect. Loss of TGF- responsiveness could be due to a reduced expression of TGF- receptors, as shown in transformed rat thyroid cell lines and in human thyroid tumors, or to alterations of other genes controlling TGF- signal transduction pathway. However, in thyroid neoplasia, a complex pattern of alterations occurring during transformation and progression has been identified. Functionally, TGF-1 acts as a tumor suppressor in the early stage of transformation or as a tumor promoter in advanced cancer. This peculiar pleiotropic behaviour of TGF- may result from cross-talk with signalling pathways mediated by other growth factors, among which EGF-like ligands play an important role. This paper reports evidences on TGF-1 and EGF systems in thyroid tumors and on the cross-talk between these growth factors in thyroid cancer.

Interleukin-1 receptors on human thyroid cells and on the rat thyroid cell line FRTL-5

Cytokine ◽  
1991 ◽  
Vol 3 (2) ◽  
pp. 125-130 ◽  
Author(s):  
M. Svenson ◽  
L. Kayser ◽  
M.B. Hansen ◽  
Å.Krogh Rasmussen ◽  
K. Bendtzen
Keyword(s):  
Cell Line ◽  
Interleukin 1 ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Rat Thyroid

Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3

2005 ◽  
Vol 288 (2) ◽  
pp. C290-C303 ◽  
Author(s):  
Tiziano Verri ◽  
Cinzia Dimitri ◽  
Sonia Treglia ◽  
Fabio Storelli ◽  
Stefania De Micheli ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Line ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Residual Fraction ◽  
Acid Transport ◽  
Thyroid Cells ◽  
Cationic Amino Acid ◽  
Rat Thyroid

Information regarding cationic amino acid transport systems in thyroid is limited to Northern blot detection of y+LAT1 mRNA in the mouse. This study investigated cationic amino acid transport in PC cell line clone 3 (PC Cl3 cells), a thyroid follicular cell line derived from a normal Fisher rat retaining many features of normal differentiated follicular thyroid cells. We provide evidence that in PC Cl3 cells plasmalemmal transport of cationic amino acids is Na+ independent and occurs, besides diffusion, with the contribution of high-affinity, carrier-mediated processes. Carrier-mediated transport is via y+, y+L, and b0,+ systems, as assessed by l-arginine uptake and kinetics, inhibition of l-arginine transport by N-ethylmaleimide and neutral amino acids, and l-cystine transport studies. y+L and y+ systems account for the highest transport rate (with y+L > y+) and b0,+ for a residual fraction of the transport. Uptake data correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, y+LAT1, y+LAT2, rBAT, and b0,+AT, an expression profile that is also shown by the rat thyroid gland. In PC Cl3 cells cationic amino acid uptake is under TSH and/or cAMP control (with transport increasing with increasing TSH concentration), and upregulation of CAT-1, CAT-2B, 4F2hc/y+LAT1, and rBAT/b0,+AT occurs at the mRNA level under TSH stimulation. Our results provide the first description of an expression pattern of cationic amino acid transport systems in thyroid cells. Furthermore, we provide evidence that extracellular l-arginine is a crucial requirement for normal PC Cl3 cell growth and that long-term l-arginine deprivation negatively influences CAT-2B expression, as it correlates to reduction of CAT-2B mRNA levels.

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