This Article Full Text Full Text (PDF) 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 Baixeras, E. Articles by Postel-Vinay, M.-C. Search for Related Content PubMed PubMed Citation Articles by Baixeras, E. Articles by Postel-Vinay, M.-C.

The Proliferative and Antiapoptotic Actions of Growth Hormone and Insulin-Like Growth Factor-1 Are Mediated through Distinct Signaling Pathways in the Pro-B Ba/F3 Cell Line¹

INSERM, U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris Cedex 15, France

Address all correspondence and request for reprints to: Dr. Marie-Catherine Postel-Vinay, INSERM, U-344, Faculté Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France. E-mail: postel-vinay{at}necker.fr

Biological actions of GH can be direct or mediated through insulin-like growth factor I (IGF-I). In the interleukin-3 (IL-3)-dependent Ba/F3 cell line, IGF-I induces cell cycle entry and proliferation. Ba/F3 cells expressing the rat GH receptor (Ba/F3 GHR cells) have been shown to escape from apoptosis and to proliferate under GH stimulation. Using the Ba/F3 GHR cell model, we sought to dissect the signals elicited specifically by IGF-I or GH. In contrast to IGF-I or IL-3, GH is able to maintain cell cycle entry of Ba/F3 GHR cells cultured for 7 days in the absence of serum. The presence of IGF-I messenger RNA was not detected by RT-PCR, and by RIA, IGF-I was not found in culture medium of Ba/F3 GHR cells, unstimulated or stimulated by GH. Moreover, the addition of an anti-IGF-I antibody that blocks IGF-I effects suggests that the actions of GH are not mediated by IGF-I, but appear to be direct. GH or IGF-I stimulation increased expression of cyclins A and D₁ with comparable kinetics, whereas expression of p21^waf1/cip1 seemed delayed in IGF-I-stimulated cells compared with that in GH-stimulated cells. Contrary to GH or IL-3, IGF-I did not induce nuclear factor-B DNA-binding activity in Ba/F3 cells. Inhibition of nuclear factor-B through expression of the mutant IB (A32/36) abrogated the GH-mediated survival signal, but did not result in alterations of the cell cycle in Ba/F3 GHR cells treated with IGF-I. Phosphatidylinositol 3-kinase was required for both survival and proliferative responses to IGF-I. Transfection of a dominant negative form of AKT (AH-AKT) resulted in suppression of IGF-I-mediated cell survival, but not of the antiapoptotic effect of GH in Ba/F3 GHR cells. Thus, GH and IGF-I are able to promote cell survival and proliferation through independent and different pathways in Ba/F3 cells.

This article has been cited by other articles:

				M. Bokhoven, S. L. Stephen, S. Knight, E. F. Gevers, I. C. Robinson, Y. Takeuchi, and M. K. Collins Insertional Gene Activation by Lentiviral and Gammaretroviral Vectors J. Virol., January 1, 2009; 83(1): 283 - 294. [Abstract] [Full Text] [PDF]

				S. Wu, D. Fadoju, G. Rezvani, and F. De Luca Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-{kappa}B p65 J. Biol. Chem., December 5, 2008; 283(49): 34037 - 34044. [Abstract] [Full Text] [PDF]

				F. Bogazzi, D. Russo, F. Raggi, F. Ultimieri, C. Urbani, M. Gasperi, L. Bartalena, and E. Martino Transgenic Mice Overexpressing Growth Hormone (GH) Have Reduced or Increased Cardiac Apoptosis through Activation of Multiple GH-Dependent or -Independent Cell Death Pathways Endocrinology, November 1, 2008; 149(11): 5758 - 5769. [Abstract] [Full Text] [PDF]

				J. L. Barclay, S. T. Anderson, M. J. Waters, and J. D. Curlewis Regulation of Suppressor of Cytokine Signaling 3 (SOC3) by Growth Hormone in Pro-B Cells Mol. Endocrinol., October 1, 2007; 21(10): 2503 - 2515. [Abstract] [Full Text] [PDF]

				G. R. Reddy, M. J. Pushpanathan, R. F. Ransom, L. B. Holzman, F. C. Brosius III, M. Diakonova, P. Mathieson, M. A. Saleem, E. O. List, J. J. Kopchick, et al. Identification of the Glomerular Podocyte as a Target for Growth Hormone Action Endocrinology, May 1, 2007; 148(5): 2045 - 2055. [Abstract] [Full Text] [PDF]

				T.-B. Liu, P. W. M. Fedak, R. D. Weisel, T. Yasuda, G. Kiani, D. A. G. Mickle, Z.-Q. Jia, and R.-K. Li Enhanced IGF-1 expression improves smooth muscle cell engraftment after cell transplantation Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2840 - H2849. [Abstract] [Full Text] [PDF]

				F. Bogazzi, F. Ultimieri, F. Raggi, D. Russo, R. Vanacore, C. Guida, S. Brogioni, C. Cosci, M. Gasperi, L. Bartalena, et al. Growth Hormone Inhibits Apoptosis in Human Colonic Cancer Cell Lines: Antagonistic Effects of Peroxisome Proliferator Activated Receptor-{gamma} Ligands Endocrinology, July 1, 2004; 145(7): 3353 - 3362. [Abstract] [Full Text] [PDF]

				L. Dalla Libera, B. Ravara, M. Volterrani, V. Gobbo, M. Della Barbera, A. Angelini, D. D. Betto, E. Germinario, and G. Vescovo Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure Am J Physiol Cell Physiol, January 1, 2004; 286(1): C138 - C144. [Abstract] [Full Text] [PDF]

				L. M. Frago, C. Paneda, S. L. Dickson, A. K. Hewson, J. Argente, and J. A. Chowen Growth Hormone (GH) and GH-Releasing Peptide-6 Increase Brain Insulin-Like Growth Factor-I Expression and Activate Intracellular Signaling Pathways Involved in Neuroprotection Endocrinology, October 1, 2002; 143(10): 4113 - 4122. [Abstract] [Full Text] [PDF]

				W.-H. Shen, J.-H. Zhou, S. R. Broussard, G. G. Freund, R. Dantzer, and K. W. Kelley Proinflammatory Cytokines Block Growth of Breast Cancer Cells by Impairing Signals from a Growth Factor Receptor Cancer Res., August 15, 2002; 62(16): 4746 - 4756. [Abstract] [Full Text] [PDF]