Document Detail


Alterations of the insulin-like growth factor system in patients with polycythemia vera.
MedLine Citation:
PMID:  11476952     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular etiology of Polycythemia vera (PV) is still undetermined. Recently, enhanced tyrosine phosphorylation of the insulin-like growth factor-I receptor (IGF-IR) has been shown in PV bone marrow progenitors and peripheral blood mononuclear cells (PBMNC), and elevated levels of IGF binding protein-1 (IGFBP-1) in the serum of PV patients have been reported. To identify further alterations of circulating IGFBPs, the IGFBP profile in the serum of 12 PV patients was compared with age- and sex-matched controls by Western ligand blot (WLB), two-dimensional WLB, IGFBP-3 immunoblot and specific RIA for IGFBP-1, -2, -3 and IGFBP-4. To elucidate a role for the IGF-IR in the pathogenesis of PV, basal and IGF-I stimulated tyrosine phosphorylation of the IGF-IR beta-subunit in PBMNC of PV patients or controls was determined by WLB. Furthermore, exons 2, 3 and 15-21 of the IGF-IR were screened for mutations by PCR-single strand conformation polymorphism analysis (PCR-SSCP). We found alterations of the IGFBP profile in the serum of eight out of 12 examined patients including elevated levels of IGFBP-1, -2 and -4, decreased levels of IGFBP-3 and an increase in IGFBP-3 fragment. However, no differences in tyrosine phosphorylation of the IGF-IR in PV patients, neither basal nor IGF-I induced, were detected. Furthermore, no mutations within the screened exons of the IGF-IR could be identified by PCR-SSCP. We conclude that there is no direct impairment of IGF-IR structure or function, but an altered IGFBP profile in a significant portion of PV patients which might contribute to the pathogenesis of PV in these patients.
Authors:
P Michl; G Spoettl; D Engelhardt; M M Weber
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  181     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-30     Completed Date:  2001-10-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  189-97     Citation Subset:  IM    
Affiliation:
Medical Department II, Klinikum Grosshadern, University of Munich, Munich, Germany. patrick.michl@medizin.uni-ulm.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Blotting, Western
Exons / genetics
Female
Humans
Insulin-Like Growth Factor Binding Proteins / blood,  metabolism*
Insulin-Like Growth Factor I / metabolism*
Leukocytes, Mononuclear / metabolism
Male
Middle Aged
Phosphorylation
Phosphotyrosine / metabolism
Polycythemia Vera / metabolism*,  physiopathology*
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Radioimmunoassay
Receptor, IGF Type 1 / genetics
Chemical
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Proteins; 21820-51-9/Phosphotyrosine; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, IGF Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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