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Gene Review

XAGE1D  -  X antigen family, member 1D

Homo sapiens

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Disease relevance of XAGE1


High impact information on XAGE1


Biological context of XAGE1

  • The XAGE family of cancer/testis-associated genes is located on chromosome Xp11.21-Xp11.22 [1].
  • Interestingly, all GAGE-like genes contain a large secondary open reading frame, coding for putative proteins homologues to the XAGE-1 primary protein [1].
  • To evaluate methylation as a potential mechanism for regulating expression of this gene, we first correlated gene methylation status (measured by sequencing of bisulfide-modified DNA and COBRA) to expression of XAGE-1 mRNA in normal and cancerous cells [6].
  • The XAGE-1 gene consists of 4 exons and is located on chromosome Xp11.21-Xp11.22 [7].
  • By serologic identification of antigens by recombinant expression cloning (SEREX) analysis using an autologous lung adenocarcinoma cell line, OU-LU-6, as a cDNA library source, we demonstrated that XAGE-1 was the dominant antigen recognized by serum from a patient [8].

Anatomical context of XAGE1

  • Further supporting the role of methylation in regulating expression of XAGE-1 were observations that treatment of 2 heavily methylated cell lines, SNU620 and HT29, with 5'-aza-deoxycytidine resulted in demethylation of XAGE-1 promoter and corresponding expression of this gene [6].
  • Finally, we cloned various segments of the CpG-rich XAGE-1 gene promoter linked to a luciferase reporter construct and transiently transfected this construct into HCT116 cells [6].

Regulatory relationships of XAGE1

  • Collectively, these studies indicate that XAGE-1 expression in normal and cancerous tissues is regulated by methylation of the CpG island in the gene promoter [6].

Other interactions of XAGE1

  • Three of these (NY-ESO-1, Lage-1, and Xage-1) were known members of the cancer/testis family of TAAs, and one other protein had previously been isolated by SEREX in cancer types other than PC [9].

Analytical, diagnostic and therapeutic context of XAGE1


  1. The XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma. Zendman, A.J., Van Kraats, A.A., Weidle, U.H., Ruiter, D.J., Van Muijen, G.N. Int. J. Cancer (2002) [Pubmed]
  2. XAGE-1, a new gene that is frequently expressed in Ewing's sarcoma. Liu, X.F., Helman, L.J., Yeung, C., Bera, T.K., Lee, B., Pastan, I. Cancer Res. (2000) [Pubmed]
  3. Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database. Brinkmann, U., Vasmatzis, G., Lee, B., Pastan, I. Cancer Res. (1999) [Pubmed]
  4. XAGE-1 expression in non-small cell lung cancer and antibody response in patients. Nakagawa, K., Noguchi, Y., Uenaka, A., Sato, S., Okumura, H., Tanaka, M., Shimono, M., Ali Eldib, A.M., Ono, T., Ohara, N., Yoshino, T., Yamashita, K., Tsunoda, T., Aoe, M., Shimizu, N., Nakayama, E. Clin. Cancer Res. (2005) [Pubmed]
  5. L552S, an alternatively spliced isoform of XAGE-1, is over-expressed in lung adenocarcinoma. Wang, T., Fan, L., Watanabe, Y., McNeill, P., Fanger, G.R., Persing, D.H., Reed, S.G. Oncogene (2001) [Pubmed]
  6. Activation of human cancer/testis antigen gene, XAGE-1, in tumor cells is correlated with CpG island hypomethylation. Lim, J.H., Kim, S.P., Gabrielson, E., Park, Y.B., Park, J.W., Kwon, T.K. Int. J. Cancer (2005) [Pubmed]
  7. Characterization of XAGE-1b, a short major transcript of cancer/testis-associated gene XAGE-1, induced in melanoma metastasis. Zendman, A.J., van Kraats, A.A., den Hollander, A.I., Weidle, U.H., Ruiter, D.J., van Muijen, G.N. Int. J. Cancer (2002) [Pubmed]
  8. Immunoscreening of a cDNA library from a lung cancer cell line using autologous patient serum: Identification of XAGE-1b as a dominant antigen and its immunogenicity in lung adenocarcinoma. Ali Eldib, A.M., Ono, T., Shimono, M., Kaneko, M., Nakagawa, K., Tanaka, R., Noguchi, Y., Nakayama, E. Int. J. Cancer (2004) [Pubmed]
  9. Serological cloning of cancer/testis antigens expressed in prostate cancer using cDNA phage surface display. Fosså, A., Alsøe, L., Crameri, R., Funderud, S., Gaudernack, G., Smeland, E.B. Cancer Immunol. Immunother. (2004) [Pubmed]
  10. Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers. Egland, K.A., Kumar, V., Duray, P., Pastan, I. Mol. Cancer Ther. (2002) [Pubmed]
  11. XAGE-1 mRNA expression in prostate cancer and antibody response in patients. Koizumi, F., Noguchi, Y., Saika, T., Nakagawa, K., Sato, S., Eldib, A.M., Nasu, Y., Kumon, H., Nakayama, E. Microbiol. Immunol. (2005) [Pubmed]
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