This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vandeput, F. Articles by Dumont, J. E. Search for Related Content PubMed PubMed Citation Articles by Vandeput, F. Articles by Dumont, J. E.

Role of the Different Mitogen-Activated Protein Kinase Subfamilies in the Stimulation of Dog and Human Thyroid Epithelial Cell Proliferation by Cyclic Adenosine 5'-Monophosphate and Growth Factors

Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium

Address all correspondence and requests for reprints to: F. Vandeput, Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Campus Erasme, Building C, Route de Lennik 808, 1070 Brussels, Belgium. E-mail: fvdeput{at}ulb.ac.be.

We have investigated the role of the different classes of MAPKs, i.e. ERKs, c-Jun N-terminal kinases (JNKs), and p38 MAPK in the proliferation of dog and human thyroid epithelial cells (thyrocytes) in primary cultures. In these cells, TSH, acting through cAMP, epidermal growth factor, hepatocyte growth factor (HGF), and phorbol 12-myristate 13-acetate induce DNA synthesis. With the exception of HGF, all of these factors require the presence of insulin for mitogenic effects to be expressed.

We found that TSH and forskolin are without effect on the phosphorylation and activity of the different classes of MAPKs. In contrast, all the cAMP-independent growth factors, whereas without effect on the phosphorylation and activity of JNKs and p38 MAPK, stimulated the ERKs. This effect was strong and sustained in response to HGF, epidermal growth factor and 12-myristate 13-acetate but weak and transient in response to insulin. Moreover, whereas in stimulated cells DNA synthesis was inhibited by PD 098059, an inhibitor of MAPK kinase 1 and consequently of ERKs, it was not modified by SB 203580, an inhibitor of p38 MAPK.

Taken together, these data 1) exclude a role of JNKs and p38 MAPK in the proliferation of dog and human thyrocytes; 2) suggest that the mitogenic action of the cAMP-independent agents requires a strong and sustained activation of both ERKs and phosphatidylinositol 3-kinase/protein kinase B as realized by HGF alone or by the other agents together with insulin; and 3) show that TSH and cAMP do not activate ERKs but that the weak activation of ERKs by insulin is nevertheless necessary for DNA synthesis to occur.

This article has been cited by other articles:

				S. Dremier, M. Milenkovic, S. Blancquaert, J. E. Dumont, S. O. Doskeland, C. Maenhaut, and P. P. Roger Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Dependent Protein Kinases, But Not Exchange Proteins Directly Activated by cAMP (Epac), Mediate Thyrotropin/cAMP-Dependent Regulation of Thyroid Cells Endocrinology, October 1, 2007; 148(10): 4612 - 4622. [Abstract] [Full Text] [PDF]

				M. J. Costa, M. Senou, F. Van Rode, J. Ruf, M. Capello, D. Dequanter, P. Lothaire, C. Dessy, J. E. Dumont, M.-C. Many, et al. Reciprocal Negative Regulation between Thyrotropin/3',5'-Cyclic Adenosine Monophosphate-Mediated Proliferation and Caveolin-1 Expression in Human and Murine Thyrocytes Mol. Endocrinol., April 1, 2007; 21(4): 921 - 932. [Abstract] [Full Text] [PDF]

				S. Paternot, J. E. Dumont, and P. P. Roger Differential Utilization of Cyclin D1 and Cyclin D3 in the Distinct Mitogenic Stimulations by Growth Factors and TSH of Human Thyrocytes in Primary Culture Mol. Endocrinol., December 1, 2006; 20(12): 3279 - 3292. [Abstract] [Full Text] [PDF]

				T Kogai, K Taki, and G A Brent Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826. [Abstract] [Full Text] [PDF]

				J. A. Gilbert, A. G. Gianoukakis, S. Salehi, J. Moorhead, P. V. Rao, M. Z. Khan, A. M. McGregor, T. J. Smith, and J. P. Banga Monoclonal pathogenic antibodies to the thyroid-stimulating hormone receptor in Graves' disease with potent thyroid-stimulating activity but differential blocking activity activate multiple signaling pathways. J. Immunol., April 15, 2006; 176(8): 5084 - 5092. [Abstract] [Full Text] [PDF]

				A. Calipel, F. Mouriaux, A.-L. Glotin, F. Malecaze, A.-M. Faussat, and F. Mascarelli Extracellular Signal-regulated Kinase-dependent Proliferation Is Mediated through the Protein Kinase A/B-Raf Pathway in Human Uveal Melanoma Cells J. Biol. Chem., April 7, 2006; 281(14): 9238 - 9250. [Abstract] [Full Text] [PDF]

				N. Fortemaison, S. Blancquaert, J. E. Dumont, C. Maenhaut, K. Aktories, P. P. Roger, and S. Dremier Differential Involvement of the Actin Cytoskeleton in Differentiation and Mitogenesis of Thyroid Cells: Inactivation of Rho Proteins Contributes to Cyclic Adenosine Monophosphate-Dependent Gene Expression but Prevents Mitogenesis Endocrinology, December 1, 2005; 146(12): 5485 - 5495. [Abstract] [Full Text] [PDF]

				C Correze, J-P Blondeau, and M Pomerance p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells Eur. J. Endocrinol., July 1, 2005; 153(1): 123 - 133. [Abstract] [Full Text] [PDF]