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Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.

Spontaneously transformed somatic thyrocyte mutants, FRTL-5/TA and FRTL-5/TP, are thyrotropin (TSH) independent for growth and show loss of the thyroid-specific phenotype, with absent thyroglobulin and thyroid peroxidase gene expression. To investigate the role of TSH-receptor (TSH-R) activation in...

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Autores principales: van der Kallen, C. J., Coes, J. H., van Grafhorst, J. P., Schuuring, E. M., Ossendorp, F. A., Thijssen, J. H., Blankenstein, M. A., de Bruin, T. W.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074668/
https://www.ncbi.nlm.nih.gov/pubmed/8761378
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author van der Kallen, C. J.
Coes, J. H.
van Grafhorst, J. P.
Schuuring, E. M.
Ossendorp, F. A.
Thijssen, J. H.
Blankenstein, M. A.
de Bruin, T. W.
author_facet van der Kallen, C. J.
Coes, J. H.
van Grafhorst, J. P.
Schuuring, E. M.
Ossendorp, F. A.
Thijssen, J. H.
Blankenstein, M. A.
de Bruin, T. W.
author_sort van der Kallen, C. J.
collection PubMed
description Spontaneously transformed somatic thyrocyte mutants, FRTL-5/TA and FRTL-5/TP, are thyrotropin (TSH) independent for growth and show loss of the thyroid-specific phenotype, with absent thyroglobulin and thyroid peroxidase gene expression. To investigate the role of TSH-receptor (TSH-R) activation in rat thyroid growth and function, binding of TSH and TSH-induced cAMP production were measured in intact cells under identical assay conditions. TSH binding did not differ in terms of affinity and receptor number and presence of 5.6 kb and 3.3 kb mRNA rat TSH-R transcripts was determined in all variants. By contrast, basal cAMP was 11-fold lower in FRTL-5/TA and 6-fold lower in FRTL-5/TP than in wild-type FRTL-5 (1.1 +/- 0.4; P < 0.01). Maximal cAMP production was similar between wild-type and cell variants and stimulation by bovine, rat and recombinant human TSH revealed normal activation patterns. Therefore, a dissociation was present between the loss of TSH control on growth and function, and the presence of a normally functioning TSH-R. Subsequent to TSH incubation FRTL-5/TP and FRTL-5/TA cells showed a different expression pattern of TSH-R and the proto oncogenes c-myc and fos than FRTL-5 wild-type. The data indicated that the cause of the TSH-independency is located down-stream of the cAMP cascade, influencing genes that control the expression of cell cycle-related proto-oncogenes and thyroid-specific genes. IMAGES:
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spelling pubmed-20746682009-09-10 Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5. van der Kallen, C. J. Coes, J. H. van Grafhorst, J. P. Schuuring, E. M. Ossendorp, F. A. Thijssen, J. H. Blankenstein, M. A. de Bruin, T. W. Br J Cancer Research Article Spontaneously transformed somatic thyrocyte mutants, FRTL-5/TA and FRTL-5/TP, are thyrotropin (TSH) independent for growth and show loss of the thyroid-specific phenotype, with absent thyroglobulin and thyroid peroxidase gene expression. To investigate the role of TSH-receptor (TSH-R) activation in rat thyroid growth and function, binding of TSH and TSH-induced cAMP production were measured in intact cells under identical assay conditions. TSH binding did not differ in terms of affinity and receptor number and presence of 5.6 kb and 3.3 kb mRNA rat TSH-R transcripts was determined in all variants. By contrast, basal cAMP was 11-fold lower in FRTL-5/TA and 6-fold lower in FRTL-5/TP than in wild-type FRTL-5 (1.1 +/- 0.4; P < 0.01). Maximal cAMP production was similar between wild-type and cell variants and stimulation by bovine, rat and recombinant human TSH revealed normal activation patterns. Therefore, a dissociation was present between the loss of TSH control on growth and function, and the presence of a normally functioning TSH-R. Subsequent to TSH incubation FRTL-5/TP and FRTL-5/TA cells showed a different expression pattern of TSH-R and the proto oncogenes c-myc and fos than FRTL-5 wild-type. The data indicated that the cause of the TSH-independency is located down-stream of the cAMP cascade, influencing genes that control the expression of cell cycle-related proto-oncogenes and thyroid-specific genes. IMAGES: Nature Publishing Group 1996-08 /pmc/articles/PMC2074668/ /pubmed/8761378 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
van der Kallen, C. J.
Coes, J. H.
van Grafhorst, J. P.
Schuuring, E. M.
Ossendorp, F. A.
Thijssen, J. H.
Blankenstein, M. A.
de Bruin, T. W.
Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title_full Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title_fullStr Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title_full_unstemmed Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title_short Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.
title_sort dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from frtl-5.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074668/
https://www.ncbi.nlm.nih.gov/pubmed/8761378
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