RESUMO
Assays relying on humoral or T-cell-based recognition of tumor antigens to identify potential targets for immunotherapy have led to the discovery of a significant number of immunogenic gene products, including cancer-testis (CT) antigens predominantly expressed in cancer cells and male germ cells. The search for cancer-specific antigens has been extended via the technique of representational-difference analysis and SK-MEL-37, a melanoma cell line expressing a broad range of CT antigens. Using this approach, we have isolated CT antigen genes, genes over-expressed in cancer, e. g., PRAME and KOC, and genes encoding neuro-ectodermal markers. The identified CT antigen genes include the previously defined MAGE-A6, MAGE-A4a, MAGE-A10, CT7/MAGE-C1, as well as a novel gene designated CT10, which shows strong homology to CT7/MAGE-C1 both at cDNA and at genomic levels. Chromosome mapping localized CT10 to Xq27, in close proximity to CT7/MAGE-C1 and MAGE-A genes. CT10 mRNA is expressed in testis and in 20 to 30% of various human cancers. A serological survey identified 2 melanoma patients with anti-CT10 antibody, demonstrating the immunogenicity of CT10 in humans.
Assuntos
Antígenos de Neoplasias/genética , Melanoma/genética , Proteínas de Neoplasias/genética , Sequência de Aminoácidos , Antígenos de Neoplasias/análise , Sequência de Bases , Mapeamento Cromossômico , Éxons , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/química , Especificidade de Órgãos , RNA Mensageiro/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Testículo/metabolismo , Transcrição Gênica , Células Tumorais CultivadasRESUMO
The serine- and arginine-rich (SR) splicing factors play an important role in both constitutive and alternative pre-mRNA splicing, and the functions of these splicing factors are regulated by phosphorylation. We have previously characterized SRPK1 (SFRSK1) and SRPK2 (SFRSK2), which are highly specific protein kinases for the SR family of splicing factors. Here we report the chromosomal localization of the mouse and human genes for both kinases. SRPK1 probes detected two loci that were mapped to mouse Chromosomes 17 and X using The Jackson Laboratory interspecific backcross DNA panel, and SRPK2 probes identified a single locus on mouse Chromosome 5. Using a somatic cell hybrid mapping panel and by fluorescence in situ hybridization, SRPK1 and SRPK2 were respectively mapped to human chromosomes 6p21.2-p21.3 (a region of conserved synteny to mouse Chromosome 17) and 7q22-q31.1 (a region of conserved synteny to mouse Chromosome 5). In addition, we also found multiple SRPK-related sequences on other human chromosomes, one of which appears to correspond to a SRPK2 pseudogene on human chromosome 8.
Assuntos
Proteínas Serina-Treonina Quinases/genética , Animais , Bandeamento Cromossômico , Mapeamento Cromossômico , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 7/genética , Cruzamentos Genéticos , Feminino , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Muridae , Splicing de RNARESUMO
CTAG was initially cloned from an esophageal squamous cell carcinoma cDNA expression library by immunoscreening with autologous patient's serum. CTAG mRNA is expressed in a proportion of human cancers in a lineage-nonspecific fashion, whereas its expression in normal tissues is restricted to testis and ovary only. This expression pattern suggests that the CTAG product (NY-ESO-1) is an aberrantly activated tumor antigen and can potentially be an antigenic target for tumor vaccination. In the present study, we isolated human genomic clones of CTAG and established its genomic organization. By somatic cell hybrid studies and fluorescence in-situ hybridization, we localized this gene to chromosome Xq28, a region that also contains members of MAGE, a gene family that encodes several immunogenic tumor antigens with the characteristic cancer/testis expression pattern.
