Document Detail

The functional -443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor.
MedLine Citation:
PMID:  18459127     Owner:  NLM     Status:  MEDLINE    
In the present report, the possible role of a recently described functional polymorphism of the osteopontin (OPN) promoter at position -443 (-443T/C) for OPN expression in melanoma cells was addressed. As shown by real-time PCR analysis, melanoma metastases that were homozygous for the -443C allele expressed significantly higher levels of OPN mRNA compared with those that were either heterozygous (-443T/C) or homozygous for the -443T allele. In line with this, immunoblotting showed significantly enhanced baseline and bFGF-induced OPN protein expression in melanoma cell lines which were homozygous for the -443C allele, compared with cell lines with other allelic variants. Similar results were obtained in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP) demonstrated binding of c-Myb to the -443 OPN promoter region, and binding could significantly be enhanced after bFGF stimulation. Moreover, as shown by electrophoretic mobility shift assays (EMSA), recombinant DNA-binding domain of c-Myb bound in a sequence-specific manner to this region. Finally, the role of c-Myb for OPN gene regulation via binding to the -443 promoter region could be further substantiated by ectopic overexpression of c-Myb in melanoma cells, using different reporter gene constructs. Taken together, it is demonstrated that the -443 promoter region exerts influence on OPN gene expression in melanoma cells, and differential binding of c-Myb transcription factor appears to play a major role in this process. These findings might be a feasible explanation for different OPN expression levels in metastatic tumors and may also have prognostic and therapeutic relevance.
Julia Schultz; Peter Lorenz; Saleh M Ibrahim; Günther Kundt; Gerd Gross; Manfred Kunz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  48     ISSN:  1098-2744     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-02-02     Completed Date:  2009-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14-23     Citation Subset:  IM    
Department of Dermatology and Venereology, University of Rostock, Rostock, Germany.
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MeSH Terms
Blotting, Western
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Neoplastic*
Immunoenzyme Techniques
Melanoma / genetics*,  metabolism,  pathology
Osteopontin / genetics*,  metabolism
Polymorphism, Genetic / genetics*
Promoter Regions, Genetic / genetics*
Protein Binding
Proto-Oncogene Proteins c-myb / antagonists & inhibitors,  genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / pharmacology
Regulatory Sequences, Nucleic Acid
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/RNA, Small Interfering; 106441-73-0/Osteopontin

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