Document Detail


Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck.
MedLine Citation:
PMID:  17273790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The opioid growth factor (OGF) is a constitutively expressed negative growth regulator whose action is mediated by the OGF receptor (OGFr). The OGF-OGFr axis tonically regulates the growth of human squamous cell carcinoma of the head and neck (SCCHN). To examine the repercussions of amplifying OGFr in SCCHN, constructs were prepared to overexpress OGFr in SCC-1 cells; six clonal lines were examined. OGFr binding assays of clonal cells revealed a 2.4- to 8.4-fold increase in binding capacity compared to wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by quantitative immunohistochemistry and Western blotting, was increased in clonal cell lines compared to controls. Under standard growth conditions the cell number of the OGFr clonal lines was reduced by 11 to 68% from the WT group, and doubling times were 7 to 67% longer. Addition of exogenous OGF further reduced (8 to 37%) cell growth of the clonal lines. Depletion of endogenous OGF with antibodies to this peptide increased growth 2-fold in cells amplifying OGFr relative to increases of 32 and 34% for the WT and EV groups, respectively. DNA synthesis of cells overexpressing OGFr was reduced from the WT group by 46 to 75%. These data indicate that the OGF receptor is integral to cell replication of SCCHN, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias.
Authors:
Patricia J McLaughlin; Michael F Verderame; Jody L Hankins; Ian S Zagon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  19     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-02     Completed Date:  2007-03-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  421-8     Citation Subset:  IM    
Affiliation:
Department of Neural and Behavioral Sciences, H109, The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. pxm9@psu.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Antibodies / pharmacology
Bromodeoxyuridine / metabolism
Carcinoma, Squamous Cell / pathology*
Cell Count
Cell Line, Tumor
Cell Proliferation / drug effects
Clone Cells
DNA, Neoplasm / biosynthesis
Down-Regulation* / drug effects
Enkephalin, Methionine / immunology,  pharmacology
Gene Expression* / drug effects
Head and Neck Neoplasms / pathology*
Humans
Kinetics
Male
Protein Binding / drug effects
Protein Transport / drug effects
Receptors, Opioid / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies; 0/DNA, Neoplasm; 0/Receptors, Opioid; 0/methionine-enkephalin receptor; 58569-55-4/Enkephalin, Methionine; 59-14-3/Bromodeoxyuridine

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


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