scholarly journals Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

2007 ◽  
Vol 14 (3) ◽  
pp. 827-837 ◽  
Author(s):  
Salvatore Ulisse ◽  
Enke Baldini ◽  
Matteo Toller ◽  
Jean-Guy Delcros ◽  
Aurélie Guého ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Coiled Coil ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Thyroid Cells ◽  
Cancer Tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

THYROID PROTEINS AND HORMONE SYNTHESIS IN HUMAN THYROID CANCER

1974 ◽  
Vol 76 (3) ◽  
pp. 651-669 ◽  
Author(s):  
Colette Thomas-Morvan ◽  
Berthe Nataf ◽  
Maurice Tubiana
Keyword(s):  
Thyroid Cancer ◽  
Organ Culture ◽  
Human Thyroid ◽  
Coupling Reactions ◽  
Variable Effect ◽  
Hormone Synthesis ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Stable Iodine

ABSTRACT Thyroid iodoproteins and hormone synthesis have been studied in vivo and in organ culture in 44 cases of thyroid cancer. In a few cases, Tg1) (17–19 S) is virtually absent; a portion of the light fractions (3–8 S), which seems to represent some precursors of Tg, incorporated in culture the 14C-amino acids. In most of the cases, the solubility profiles, sedimentation patterns as well as electrophoretic migration of proteins were normal. The content of Tg and the concentration of stable iodine (127I) in Tg are less than that of "normal" tissues, and the deficiency in iodination appears to be more pronounced than the depression of the Tg synthesis. Most frequently the radioiodine uptake is very low and most of the iodine remains in the gland as iodide and MIT. In those tissues which organify radioiodine, it is incorporated into tyrosine molecules and is metabolized to the stage of iodothyronines (T4 + T3); there must then be little or no defect in coupling reactions. There is a linear relation between the concentration of stable iodine in Tg and the level of hormone synthesis, as we have found in "normal" gland and benign thyroid diseases. These results suggest that the overall disorder seen in thyroid cancer tissues appears to involve one of the initial steps of hormone synthesis. The very low mean iodination of Tg in these tissues suggests a great heterogeneity in the functional activity throughout the tumour. TSH has a very variable effect on thyroid cancer tissues maintained in organ culture: in 46 % of the cases the hormone has no effect. In some instances TSH may significantly increase the incorporation of radioiodine into soluble iodoproteins, Tg as well as the albumin fraction.

scholarly journals MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle

2007 ◽  
Vol 14 (3) ◽  
pp. 791-798 ◽  
Author(s):  
Rosa Visone ◽  
Lucia Russo ◽  
Pierlorenzo Pallante ◽  
Ivana De Martino ◽  
Angelo Ferraro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein A ◽  
Thyroid Tissue ◽  
Inverse Correlation ◽  
Bioinformatic Analysis ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Protein Levels ◽  
Thyroid Papillary

We have recently reported that MicroRNAs (miR)-221 and miR-222 were up-regulated in human thyroid papillary carcinomas in comparison with the normal thyroid tissue. Bioinformatic analysis proposed the p27Kip1 protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster. Here, we report that the enforced expression of miR-221 and miR-222 was able to reduce p27Kip1 protein levels in thyroid carcinoma and HeLa cells in the absence of significant changes in specific p27Kip1 mRNA levels. This effect is direct as miR-221 and miR-222 negatively regulate the expression of the 3′-untranslated region-based reporter construct from the p27Kip1 gene, and is dependent on two target sites in this region. Consistent with these results, an enforced expression of the miR-221 and miR-222 induced the thyroid papillary carcinoma cell line (TPC-1) to progress to the S phase of the cell cycle. It is likely that the negative regulation of p27Kip1 by miR-221 and miR-222 might also have a role in vivo since we report an inverse correlation between miR-221 and miR-222 up-regulation and down-regulation of the p27Kip1 protein levels in human thyroid papillary carcinomas. Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27Kip1 protein expression, and thereby, the cell cycle.

Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells

2017 ◽  
Vol 115 ◽  
pp. 288-298 ◽  
Author(s):  
Chieh-Hsiang Lu ◽  
Shu-Hsin Chen ◽  
Yi-Sheng Chang ◽  
Yi-Wen Liu ◽  
Jin-Yi Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Thyroid Cancer ◽  
Therapeutic Agent ◽  
Human Thyroid ◽  
Cycle Arrest ◽  
Thyroid Cancer Cells ◽  
Program Cell Death

scholarly journals Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG

2012 ◽  
Vol 198 (4) ◽  
pp. 591-605 ◽  
Author(s):  
Amy B. Foraker ◽  
Stéphane M. Camus ◽  
Timothy M. Evans ◽  
Sophia R. Majeed ◽  
Chih-Ying Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Coiled Coil ◽  
S Phase ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Multipolar Spindles ◽  
Associated Proteins ◽  
A Cell ◽  
Spindle Stability

Clathrin depletion by ribonucleic acid interference (RNAi) impairs mitotic spindle stability and cytokinesis. Depletion of several clathrin-associated proteins affects centrosome integrity, suggesting a further cell cycle function for clathrin. In this paper, we report that RNAi depletion of CHC17 (clathrin heavy chain 17) clathrin, but not the CHC22 clathrin isoform, induced centrosome amplification and multipolar spindles. To stage clathrin function within the cell cycle, a cell line expressing SNAP-tagged clathrin light chains was generated. Acute clathrin inactivation by chemical dimerization of the SNAP-tag during S phase caused reduction of both clathrin and ch-TOG (colonic, hepatic tumor overexpressed gene) at metaphase centrosomes, which became fragmented. This was phenocopied by treatment with Aurora A kinase inhibitor, suggesting a centrosomal role for the Aurora A–dependent complex of clathrin, ch-TOG, and TACC3 (transforming acidic coiled-coil protein 3). Clathrin inactivation in S phase also reduced total cellular levels of ch-TOG by metaphase. Live-cell imaging showed dynamic clathrin recruitment during centrosome maturation. Therefore, we propose that clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin–ch-TOG–TACC3 complex.

scholarly journals Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4266
Author(s):  
Fang-Ping Kung ◽  
Yun-Ping Lim ◽  
Wen-Ying Chao ◽  
Yi-Sheng Zhang ◽  
Hui-I Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Thyroid ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Apoptosis Pathway

Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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