Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer Journal Article
| Authors: | Güre, A. O.; Stockert, E.; Scanlan, M. J.; Keresztes, R. S.; Jäger, D.; Altorki, N. K.; Old, L. J.; Chen, Y. T. |
| Article Title: | Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer |
| Abstract: | Serological analysis of expression cDNA libraries (SEREX) derived from two small cell lung cancer (SCLC) cell lines using pooled sera of SCLC patients led to the isolation of 14 genes, including 4 SOX group B genes (SOX1, SOX2, SOX3, and SOX21) and ZIC2. SOX group B genes and ZIC2 encode DNA-binding proteins; SOX group B proteins regulate transcription of target genes in the presence of cofactors, whereas ZIC2 is also suspected to be a transcriptional regulator. These genes are expressed at early developmental stages in the embryonic nervous system, but are down-regulated in the adult. Although SOX2 mRNA can be detected in some adult tissues, ZIC2 is expressed only in brain and testis, and SOX1, SOX3, and SOX21 transcripts are not detectable in normal adult tissues. Of SCLC cell lines tested, 80% expressed ZIC2 mRNA, and SOX1, SOX2, and SOX3 expression was detected in 40%, 50%, and 10%, respectively. SOX group B and ZlC2 antigens elicited serological responses in 30-40% of SCLC patients in this series, at titers up to 1:106. In sera from 23 normal adults, no antibody was detected against SOX group B or ZlC2 proteins except for one individual with low-titer anti-SOX2 antibody. Seroreactivity against SOX1 and 2 was consistently higher titered than SOX3 and 21 reactivity, suggesting SOX1 and/or SOX2 as the main antigens eliciting anti-SOX responses. Although paraneoplastic neurological syndromes have been associated with several SCLC antigens, neurological symptoms have not been observed in patients with anti-SOX or anti-ZlC2 antibodies. |
| Keywords: | adult; controlled study; human tissue; unclassified drug; dna binding protein; human cell; reverse transcription polymerase chain reaction; embryo; lung neoplasms; nerve tissue proteins; tumor cells, cultured; tumor antigen; transcription factors; lung small cell cancer; transcription regulation; amino acid sequence; molecular sequence data; sequence homology, amino acid; antigens, neoplasm; messenger rna; immunogenicity; nucleotide sequence; base sequence; dna primers; paraneoplastic syndrome; humoral immunity; nerve protein; nervous system development; serology; antibodies, neoplasm; antibody titer; northern blotting; carcinoma, small cell; dna library; humans; human; priority journal; article; protein sox; protein zic2 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 97 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2000-04-11 |
| Start Page: | 4198 |
| End Page: | 4203 |
| Language: | English |
| DOI: | 10.1073/pnas.97.8.4198 |
| PUBMED: | 10760287 |
| PROVIDER: | scopus |
| PMCID: | PMC18195 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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