Expression of β‐arrestins in toxic and cold thyroid nodules

Voigt, Carsten; Holzapfel, H.; Paschke, Ralf

doi:10.1016/s0014-5793(00)02302-4

Cited by 31 publications

(24 citation statements)

References 39 publications

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“…An upregulation of phosphodiesterases by cAMP has been observed previously in thyroid cells in vitro as well as in other systems (Nilson et al, 1980;Persani et al, 2000). Negative feedback in the adenoma cells is further provided by an upregulation of GRK5, which desensitizes the TSH receptor (Voigt et al, 2004), and by a minor downregulation of adenylylcyclase (Eszlinger et al, 2004). Cell heterogeneity and the great sensitivity of the cells to small cAMP rises (Neve and Dumont, 1970;Ketelbant-Balasse et al, 1976) might explain how the slightly increased averaged cAMP levels can sustain the increased activity and growth of thyrocytes.…”

Section: Discussionmentioning

confidence: 55%

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Wattel¹,

Mircescu²,

Venet³

et al. 2005

Oncogene

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The purpose of this study was to use the microarray technology to define expression profiles characteristic of thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed on a series of separated adenomas and their normal counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18 000 spots (analysis II). Results for genes present on the two arrays corroborated and several gene regulations previously determined by Northern blotting or microarrays in similar lesions were confirmed. Five overexpressed and 24 underexpressed genes were also confirmed by real-time RT-PCR in some of the samples used for microarray analysis, and in additional tumor specimens. Our results show: (1) a change in the cell populations of the tumor, with a marked decrease in lymphocytes and blood cells and an increase in endothelial cells. The latter increase would correspond to the establishment of a close relation between thyrocytes and endothelial cells and is related to increased N-cadherin expression. It explains the increased blood flow in the tumor; (2) a homogeneity of tumor samples correlating with their common physiopathological mechanism: the constitutive activation of the thyrotropin (TSH)/cAMP cascade; (3) a low proportion of regulated genes consistent with the concept of a minimal deviation tumor; (4) a higher expression of genes coding for specific functional proteins, consistent with the functional hyperactivity of the tumors; (5) an increase of phosphodiesterase gene expression which explains the relatively low cyclic AMP levels measured in these tumors; (6) an overexpression of antiapoptotic genes and underexpression of proapoptotic genes compatible with their low apoptosis rate; (7) an overexpression of N-cadherin and downregulation of caveolins, which casts doubt about the use of these expressions as markers for malignancy.Oncogene (2005) 24, 6902-6916.

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Section: Discussionmentioning

confidence: 55%

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Wattel¹,

Mircescu²,

Venet³

et al. 2005

Oncogene

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“…Finally, we found that our ATC/PDTC series had a deregulation of critical genes for thyroid hormone synthesis, such as the overexpression of ARRB2 (b-arrestin 2; Voigt et al, 2000), which is implicated in the desensitization of thyroid-stimulating hormone receptors (TSHR), the underexpression of RAB5A, which participates in the thyroglobulin production (TG; Croizet-Berger et al, 2002), and a diminished expression of TG and PAX8, which has also been observed before in ATC/PDTC series (Onda et al, 2004). Furthermore, the expression of HHEX, a gene related to thyroid morphogenesis and differentiation, was decreased in ATC/PDTC.…”

Section: Discussionmentioning

confidence: 86%

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

et al. 2007

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Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with >2-fold difference in absolute values and false discovery rate of o0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-b signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.

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“…These different results can most likely be explained by defects in the RGS regulation pathway or by additional counter-regulatory pathways which occur in the chronically proliferating hot thyroid nodules. The increased expression of b-arrestin 2 in hot thyroid nodules (46) is possibly an example of such an additional counter-regulation. b-arrestin 2 desensitizes the TSHR followed by a blocked G protein coupling.…”

Section: Discussionmentioning

confidence: 99%

RGS 2 expression is regulated by TSH and inhibits TSH receptor signaling

Eszlinger

Holzapfel²,

Voigt³

et al. 2004

European Journal of Endocrinology

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Objective: A new family of guanosine triphosphatase-activating proteins known as regulators of G protein signaling (RGS) has been found to regulate the desensitization of several G protein-coupled ligandinduced processes. The expression of nine RGS mRNAs was found in human thyroid tissue (RGS 2,3,5,6,9,10,12, 14 and 16). At present, little is known as to whether any of the RGS proteins play a role in TSH signaling. Design and methods: To explore the involvement of RGS proteins in the regulation of TSH receptor (TSHR) signal transduction, mRNA expression levels of the RGS proteins were analyzed after TSH stimulation of human thyroid primary cultures by real-time RT-PCR. Furthermore, the effects of RGS 2 expression on TSHR signaling (cAMP-, inositol-3-phosphate accumulation, TSHR cell surface expression) were studied in COS-7 cells. Results: Only RGS 2 mRNA was found to be regulated by TSH in thyroid primary cultures. Co-expression of RGS 2 and TSHR in COS-7 cells reduced the TSHR signaling via inositol-3-phosphate but not via cAMP after stimulation with TSH. Conclusion: TSH-dependent RGS 2 mRNA expression and the suppression of TSH-G q a signaling by the overexpression of RGS 2 imply that RGS 2 is involved in TSHR-induced G q signal transduction.European Journal of Endocrinology 151 383-390

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Expression of β‐arrestins in toxic and cold thyroid nodules

Cited by 31 publications

References 39 publications

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information

RGS 2 expression is regulated by TSH and inhibits TSH receptor signaling

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