Cancer-testis antigens and ING1 tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene.
SEREX (serological analysis of recombinant tumor cDNA expression libraries) has been applied to several different tumor types and has led to the identification of a wide range of tumor antigens. In this study, a breast cancer library and a normal testicular library were analyzed using autologous and allogeneic breast cancer sera. Thirty genes were isolated, including 27 known genes and 3 previously unknown genes. Among the known genes, two cancer-testis (CT) antigens, NY-ESO-1 and SSX2, previously defined by SEREX analysis, were found. In addition, ING1, a candidate breast cancer suppressor gene, was isolated. This ING1 gene product was also recognized by 2 of 14 allogeneic sera from breast cancer patients but not 12 normal adult sera. Comparison of ING1 cDNA from normal and tumor tissues showed no mutation in the index breast cancer case and revealed the presence of at least three different mRNA transcripts with variable transcription initiation sites and exon usage. Tissue-specific expression of these transcripts was found in normal tissues and tumor cell line mRNAs. Furthermore, a novel gene, designated as ING2, sharing 76% nucleotide homology with ING1 was identified in the breast cancer cDNA library. The basis of the immunogenicity of ING1 and the biological role of ING1 and ING2 need further exploration.
Jäger
D
D
Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
Stockert
E
E
Scanlan
M J
MJ
Güre
A O
AO
Jäger
E
E
Knuth
A
A
Old
L J
LJ
Chen
Y T
YT
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D005260:Female; D015723:Gene Library; D016147:Genes, Tumor Suppressor; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013737:Testis / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C093962:synovial sarcoma X breakpoint proteins