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This Article Accepted manuscript (PDF) Supplementary figures All Versions of this Article: JOE-07-0562v1 198/1/101    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Métayé, T. Articles by Perdrisot, R Search for Related Content PubMed PubMed Citation Articles by Métayé, T. Articles by Perdrisot, R

T Métayé, Biophysique, Centre Hospitalier universitaire de Poitiers, Poitiers Cedex, 86021, France
P Levillain, Anatomie et cytologie pathologiques, CHU de Poitiers, Poitiers, France
J Kraimps, Chirurgie endocrinienne, CHU de Poitiers, Poitiers, France
R Perdrisot, Medicine Nuclaire et Biophysique, CHU de Poitiers, Poitiers, France

Correspondence: Thierry Métayé, Email: t.metaye{at}chu-poitiers.fr

Abstract

Thyrotropin (TSH), via its G protein-coupled receptor, activates cell growth of both benign and malignant thyroid tumours. G protein-coupled receptor kinase 2 (GRK2) has been reported to regulate the TSH receptor but its role in cancer is unknown. To determine a possible function for GRK2 in the growth process of thyroid cancers, we analysed its expression in normal and tumoral thyroid tissues, and studied thyroid cancer cell line proliferation after GRK2 overexpression. Thirty one thyroid tissues, including 16 nonmedullary thyroid cancers and 15 adjacent normal tissues were analysed by immunohistochemistry. Five paired tissues were also studied by Western blotting and for GRK2 enzymatic activity. Immunohistochemical staining showed an increase of GRK2 in thyroid cancers including papillary, follicular and anaplastic types, compared with their adjacent normal tissues. Immunoblot analysis and GRK2 enzymatic activity measurement confirmed immunohistochemical study. TSH and TSH in association with insulin or IGF-I stimulated GRK2 protein accumulation in normal human thyroid cells in primary culture. TSH effect on GRK2 expression was mimicked by forskolin. After GRK2 overexpression in two poorly differentiated thyroid cell lines, all the clones showed a significant reduction in cell proliferation, ranging from 28% to 65% inhibition compared with vector alone after 96-h culture. In conclusion, thyroid mitogenic factor-stimulated GRK2 accumulation may explain, in part, high GRK2 levels in differentiated carcinoma, because TSH, insulin or IGF-I are known to be involved in thyroid cancer progression. Surprisingly, instead of stimulating, GRK2 reduced cell proliferation, revealing a new role for this kinase in the growth of thyroid cancers.