Document Detail


Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line.
MedLine Citation:
PMID:  10809229     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-kappaB (NF-kappaB), which has been shown to promote cell survival, was sustained in Ba/F3 GHR cells, whereas no NF-kappaB activation was detected in parental Ba/F3 cells in the absence of growth factor. Furthermore, addition of GH induced NF-kappaB DNA binding activity in Ba/F3 GHR cells. Overexpression of the mutated IkappaB alpha (A32/36) protein, known to inhibit NF-kappaB 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-kappaB and sustained levels of the antiapoptotic proteins Bcl-2 and Bag-1.
Authors:
S Jeay; G E Sonenshein; M C Postel-Vinay; E Baixeras
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  14     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  650-61     Citation Subset:  IM    
Affiliation:
INSERM Unité 344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Autocrine Communication
Carrier Proteins / biosynthesis
Cattle
Cell Cycle / drug effects
Cell Line
Culture Media / pharmacology
DNA, Complementary / genetics
DNA-Binding Proteins / genetics,  physiology
Depression, Chemical
Dimerization
Genes, bcl-2
Growth Hormone / antagonists & inhibitors,  pharmacology*
Hematopoietic Stem Cells / cytology,  drug effects*
I-kappa B Proteins*
Interleukin-3 / pharmacology*
Mice
NF-kappa B / physiology*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Rats
Receptors, Somatotropin / drug effects*,  genetics,  metabolism
Transcription Factors
Transcription, Genetic / drug effects*
Transfection
bcl-X Protein
Grant Support
ID/Acronym/Agency:
CA-36355/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BCL2-associated athanogene 1 protein; 0/Bcl2l1 protein, mouse; 0/Bcl2l1 protein, rat; 0/Carrier Proteins; 0/Culture Media; 0/DNA, Complementary; 0/DNA-Binding Proteins; 0/I-kappa B Proteins; 0/Interleukin-3; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Somatotropin; 0/Transcription Factors; 0/bcl-X Protein; 139874-52-5/NF-kappaB inhibitor alpha; 9002-72-6/Growth Hormone

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