Disease relevance of CSAG2

• CSAGE and TRAG-3 are expressed in chondrosarcoma, melanoma, and cartilage and testis, but not in other normal tissues [1].
• TRAG-3 has been reported to be a cancer/testis antigen [1].
• Northern analysis demonstrates that TRAG-3 is overexpressed in the taxol-resistant breast cancer cell line MDA 435TR as well as the doxorubicin-resistant multiple myeloma cell lines 8226/DOX40 and 8226/MDR10V [2].
• TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line [2].
• TRAG-3 is a cancer germline Ag expressed by tumors of different histological types including the majority of melanoma, breast, and lung cancers [3].

High impact information on CSAG2

• The taxol resistance gene TRAG-3 was initially isolated from cancer cell lines that became resistant to taxol in vitro [3].
• All stage IV melanoma patients with TRAG-3-expressing tumors developed spontaneous CD4+ T cell responses against TRAG-3, demonstrating its strong immunogenicity [3].
• Altogether, our data define a novel profile of spontaneous immune responses to cancer germline Ag-expressing tumors, showing that spontaneous TRAG-3-specific CD4+ T cells are directed against a single immunodominant epitope and exist independently of Ab responses [3].
• In the present study, we report that patients with stage IV melanoma and breast cancers developed spontaneous IFN-gamma-producing CD4+ T cell responses against a single immunodominant and promiscuous peptide epitope from TRAG-3 presented in the context of multiple HLA-DR molecules [3].
• The TRAG-3-specific CD4+ T cells and clones were expanded in vitro and recognized not only peptide pulsed APCs but also autologous dendritic cells (DCs) loaded with the TRAG-3 protein [3].

Biological context of CSAG2

• In summary, TRAG-3 is a novel gene whose expression is associated with the chemotherapy-resistant and neoplastic phenotype [2].
• The nucleotide sequence of the TRAG-3 cDNA contains an open reading frame of 333bp that predicts for a protein product of 110 amino acids [2].
• A GenBank search identifies a cosmid clone containing a genomic sequence corresponding to that of TRAG-3 [2].
• BACKGROUND: We have identified a novel cancer/testis antigen, TRAG-3, (Taxol Resistance Associated Gene-3) that was initially discovered in search for new genes involved in drug resistance by differential display [4].
• Treatment of a TRAG-3-silenced cell line H23 with the demethylating reagent 5-aza-cytosine reduced DNA methylation and induced TRAG-3 expression in a dose-dependent manner [5].

Anatomical context of CSAG2

• In comparison to the parental line, SKOV-3, TRAG-3 mRNA is overexpressed in the taxol-resistant cell line SKOV-3TR [2].
• Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TRAG-3 antigen [6].

Other interactions of CSAG2

• The TRAG-3 expression significantly correlated with the expression of MAGE-3 in esophageal cancer (p<0.05) [7].
• To distinguish between these two hypotheses, expression of the genes that flank TRAG-3 was evaluated, namely the Centrin 2 gene and several members of the MAGE gene cluster [8].
• The identified HLA-A*02.01-restricted TRAG-3-derived epitopes are targets for spontaneous immune responses in breast cancer, hematopoietic cancer, and melanoma patients [9].

Analytical, diagnostic and therapeutic context of CSAG2

• MATERIALS AND METHODS: Northern and RT-PCR technologies were used to evaluate TRAG-3 expression in numerous cell lines and tumor tissue [4].
• CONCLUSIONS: Because TRAG-3 is a cancer/testis antigen expressed in most melanomas and half of non-small cell lung carcinomas, identification of the TRAG-3/HLA-A2.1 peptide ILLRDAGLV may facilitate peptide-based specific immunotherapy for various histological tumors [6].

References