Growth hormone prevents apoptosis through activation of nuclear factor-κB in interleukin-3-dependent Ba/F3 cell line

S Jeay, GE Sonenshein, MC Postel-Vinay… - Molecular …, 2000 - academic.oup.com
S Jeay, GE Sonenshein, MC Postel-Vinay, E Baixeras
Molecular endocrinology, 2000academic.oup.com
Abstract The pro-B Ba/F3 cell line requires interleukin-3 and serum for growth, and their
removal results in cell apoptosis. Ba/F3 cells transfected with the GH receptor (GHR) cDNA
become able to proliferate in response to GH. To investigate the role of GH in the control of
apoptosis, Ba/F3 cells expressing either the wild-type rat GHR (Ba/F3 GHR) or a mutated rat
GHR (Ba/F3 ILV/T) were used. We show that Ba/F3 GHR cells, but not parental Ba/F3 or
Ba/F3 ILV/T cells, were able to survive in the absence of growth factor. Furthermore, an …
Abstract
The pro-B Ba/F3 cell line requires interleukin-3 and serum for growth, and their removal results in cell apoptosis. Ba/F3 cells transfected with the GH receptor (GHR) cDNA become able to proliferate in response to GH. To investigate the role of GH in the control of apoptosis, Ba/F3 cells expressing either the wild-type rat GHR (Ba/F3 GHR) or a mutated rat GHR (Ba/F3 ILV/T) were used. We show that Ba/F3 GHR cells, but not parental Ba/F3 or Ba/F3 ILV/T cells, were able to survive in the absence of growth factor. Furthermore, an autocrine/paracrine mode of GH action was suggested by the demonstration that Ba/F3 cells produce GH, and that addition of GH antagonists (B2036 and G120K) promotes apoptosis of Ba/F3 GHR cells. Consistent with survival, the levels of both antiapoptotic proteins Bcl-2 and Bag-1 were maintained in Ba/F3 GHR cells, but not in parental Ba/F3 cells upon growth factor deprivation. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB), which has been shown to promote cell survival, was sustained in Ba/F3 GHR cells, whereas no NF-κB activation was detected in parental Ba/F3 cells in the absence of growth factor. Furthermore, addition of GH induced NF-κB DNA binding activity in Ba/F3 GHR cells. Overexpression of the mutated IκBα (A32/36) protein, known to inhibit NF-κB activity, resulted in death of growth factor-deprived Ba/F3 GHR cells, and addition of GH was no longer able to rescue these cells from apoptosis. Together, our results provide evidence for a new GH-mediated pathway that initiates a survival signal through activation of the transcription factor NF-κB and sustained levels of the antiapoptotic proteins Bcl-2 and Bag-1.
Oxford University Press