Document Detail

Identification of a point mutation in the folate receptor gene that confers a dominant negative phenotype.
MedLine Citation:
PMID:  7850798     Owner:  NLM     Status:  MEDLINE    
UM-SCC-38 cells, a squamous cell carcinoma cell line of the head and neck, express limited amounts of folate receptor alpha antigen which is not capable of binding either folic acid or 5-methyltetrahydrofolic acid. Three distinct mutations in the open reading frame of the folate receptor were identified. We now show that the three mutants are nonfunctional with respect to folic acid binding because the protein products do not bind folate. Additionally, a study of MA104 cells (a receptor-positive cell line) transfected with each mutant was done. Expression of one mutant, FR-67, results in a dominant negative phenotype because folate binding is significantly reduced although membrane antigen is significantly increased. Coexpression of FR-67 and the normal protein in MA104 cells also results in large, bright clusters of receptor protein inside the cell around the nucleus when visualized using indirect immunofluorescence. These clusters are not found in cells that express either normal or FR-67 protein alone. In conclusion, this study provides the first evidence of a mutant folate receptor protein capable of affecting normal receptor function in a dominant negative manner.
R B Orr; B A Kamen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  55     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-14     Completed Date:  1995-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  847-52     Citation Subset:  IM    
Department of Pediatrics and Pharmacology, University of Texas Southwestern Medical Center at Dallas 75235-9063.
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MeSH Terms
CHO Cells / physiology
Carcinoma, Squamous Cell / genetics,  ultrastructure
Carrier Proteins / biosynthesis,  genetics*,  metabolism*
DNA, Complementary / genetics
Folic Acid / metabolism
Genes, Dominant
Glycosylphosphatidylinositols / metabolism
Point Mutation*
Receptors, Cell Surface*
Tetrahydrofolates / metabolism
Reg. No./Substance:
0/Carrier Proteins; 0/DNA, Complementary; 0/Glycosylphosphatidylinositols; 0/Receptors, Cell Surface; 0/Tetrahydrofolates; 0/folate-binding protein; 10028-17-8/Tritium; 134-35-0/5-methyltetrahydrofolate; 59-30-3/Folic Acid

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