title: Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers.
abstract: Cancer testis (CT) antigens have an expression pattern that is predominantly restricted to testis in normal tissues, yet they are expressed in many different histological types of cancers. One previously described member of the CT antigen family, XAGE-1, was shown to be expressed in Ewing's sarcomas and rhabdomyosarcomas. Here we show that XAGE-1 is also expressed in breast cancer, prostate cancer, and different types of lung cancers, including lung squamous cell carcinoma, adenocarcinoma, small cell lung carcinoma, and non-small cell lung carcinoma. In addition, XAGE-1 mRNA was present in ovarian cancer, melanoma, glioblastoma, T-cell lymphoma, chronic myelogenous leukemia, and histiocytic lymphoma cell lines. We also characterized the XAGE-1 transcript by primer extension analysis and found that transcription of the XAGE-1 gene is initiated from two distinct start sites, resulting in two overlapping transcripts, XAGE-1a and XAGE-1b. XAGE-1a contains two in-frame ATG translational start codons; whereas XAGE-1b initiates downstream of the first ATG start codon. Our results suggest that XAGE-1b is the dominant transcript, and that translation begins with the second ATG start codon, producing a 9 kDa protein. Because XAGE-1 is expressed in such a diverse range of cancers, it has potential to be used as a target for many cancer immunotherapies.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA.
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Egland
authors.forename: Vasantha
authors.initials: V
authors.lastname: Kumar
authors.forename: Paul
authors.initials: P
authors.lastname: Duray
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D017931:DNA Primers / Q000494:pharmacology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D017931:DNA Primers; D012333:RNA, Messenger; C413656:XAGE1A protein, human; D012313:RNA