Translation initiation factor eIF-4G is immunogenic, overexpressed, and amplified in patients with squamous cell lung carcinoma.
BACKGROUND
Recently, the authors reported identification and cloning of several novel immunogenic antigens in squamous cell lung carcinoma. Of 14 corresponding genes, 9 mapped in an amplified chromosomal region with the gene for eIF-4G that was amplified most frequently.


METHODS
Recombinant eIF-4G was expressed in E. coli and screened with sera from patients with squamous cell carcinoma of the lung and of the head and neck. Protein extracts from squamous cell carcinoma tissues were analyzed for eIF-4G expression by Western blot analysis. Mutation analysis was performed using an automatic DNA sequencer.


RESULTS
The authors screened a spectrum of 33 heterologous sera from lung carcinoma patients and detected antibodies against eIF-4G in 5 of these sera (15%). They found no immune response to eIF-4G in 17 sera from squamous cell carcinoma tissues derived from the head and neck. In addition, no antibodies were found to eIF-4G in a group of 17 control sera from individuals without known tumor formation. Sequence analysis of the eIF-4G gave no indication of mutations. To analyze the expression of eIF-4G, a monoclonal antibody was used. Western blot analysis clearly showed overexpression in the tumor tissue compared with the corresponding normal lung tissues.


CONCLUSIONS
The translation initiation factor eIF-4G is the first protein in which the gene shows amplification, has increased expression in a human tumor, and induces an immune response in patients. eIF-4G lends itself as a marker for the diagnosis of and possibly as a future therapeutic target in patients with squamous cell lung carcinoma.
Bauer
C
C
Department of Human Genetics, Medical School, University of Saarland, 66421 Homburg/Saar, Germany.
Diesinger
I
I
Brass
N
N
Steinhart
H
H
Iro
H
H
Meese
E U
EU
D000917:Antibody Formation; D000951:Antigens, Neoplasm; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification; D018076:DNA, Complementary; D039603:Eukaryotic Initiation Factor-4G; D005784:Gene Amplification; D005819:Genetic Markers; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D039603:Eukaryotic Initiation Factor-4G; D005819:Genetic Markers; D010448:Peptide Initiation Factors; D004247:DNA