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Gene Review

EBAG9  -  estrogen receptor binding site associated,...

Homo sapiens

Synonyms: Cancer-associated surface antigen RCAS1, EB9, Estrogen receptor-binding fragment-associated gene 9 protein, PDAF, RCAS1, ...
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Disease relevance of EBAG9

  • The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) has been identified as a primary estrogen-responsive gene in human breast cancer MCF7 cells [1].
  • A high expression of EBAG9 has been observed in invasive breast cancer and advanced prostate cancer, suggesting a tumor-promoting role of the protein in malignancies [1].
  • Here we show that intratumoral (i.t.) administration of small interfering RNA against EBAG9 exerted overt regression of tumors following s.c. implantation of murine renal cell carcinoma (RCC) Renca cells [1].
  • Twenty-eight of 29 were T1/T2 stage carcinomas (<5 cm in diameter), whereas one third (21 of 61) of the tumors in which CMYC was increased but EBAG9 was not, were advanced T3-stage tumors (P = 0.0012) [2].
  • EBAG9 was more frequently expressed at sites of capsular penetration (79%) and lymph node metastasis (100%) compared to intracapsular primary tumors (54%) (p = 0.0264 and 0.0048, respectively) [3].

Psychiatry related information on EBAG9


High impact information on EBAG9

  • Given these results, tumor cells may evade immune surveillance by expression of RCAS1, which would suppress clonal expansion and induce apoptosis in RCAS1 receptor-positive immune cells [6].
  • RCAS1 acts as a ligand for a putative receptor present on various human cell lines and normal peripheral lymphocytes such as T, B and NK cells [6].
  • Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1 [6].
  • In contrast, RCAS-c-myc induced endocrine tumors exclusively, as determined by histology and detection of differentiation markers [7].
  • Posterior lateral plate mesoderm normally forms blood, but coculture of this tissue with anterior endoderm or infection with RCAS-crescent induces formation of beating heart muscle and represses formation of blood [8].

Biological context of EBAG9


Anatomical context of EBAG9


Associations of EBAG9 with chemical compounds


Regulatory relationships of EBAG9

  • RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) and Fas ligand (FasL) are present in neoplastic cells, induce apoptosis of NK/T cells, and play a role in immune evasion [17].

Other interactions of EBAG9

  • Then cDNAs associated with two of them, EB1 and EB9, were isolated from libraries of human placenta and MCF-7 cells derived from a human breast cancer, respectively [18].
  • The mean RCAS1/GAPDH ratio of tumors (0.7) was not different from that of non-cancerous epithelia (0.7, p=0.715) [19].
  • The Role of RCAS1 and oxytocinase in immune tolerance during pregnancy [20].
  • Univariate analysis for a recurrence-free prognosis demonstrated that antibody detection of p53 expression (p=0.0333) and expression of RCAS1 (p=0.0008) is correlated with a significantly higher potential of recurrence [21].
  • EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) alpha labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3(+) T lymphocytes (P = 0.0025) [14].

Analytical, diagnostic and therapeutic context of EBAG9


  1. Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma. Ogushi, T., Takahashi, S., Takeuchi, T., Urano, T., Horie-Inoue, K., Kumagai, J., Kitamura, T., Ouchi, Y., Muramatsu, M., Inoue, S. Cancer Res. (2005) [Pubmed]
  2. Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers. Tsuneizumi, M., Emi, M., Nagai, H., Harada, H., Sakamoto, G., Kasumi, F., Inoue, S., Kazui, T., Nakamura, Y. Clin. Cancer Res. (2001) [Pubmed]
  3. EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer. Takahashi, S., Urano, T., Tsuchiya, F., Fujimura, T., Kitamura, T., Ouchi, Y., Muramatsu, M., Inoue, S. Int. J. Cancer (2003) [Pubmed]
  4. Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Flamme, I., von Reutern, M., Drexler, H.C., Syed-Ali, S., Risau, W. Dev. Biol. (1995) [Pubmed]
  5. Prognostic Significance of RCAS1 Expression in Relation to the Infiltration of Dendritic Cells and Lymphocytes in Patients with Esophageal Carcinoma. Tsujitani, S., Saito, H., Oka, S., Sakamoto, T., Kanaji, S., Tatebe, S., Ikeguchi, M. Dig. Dis. Sci. (2007) [Pubmed]
  6. Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nakashima, M., Sonoda, K., Watanabe, T. Nat. Med. (1999) [Pubmed]
  7. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer. Lewis, B.C., Klimstra, D.S., Varmus, H.E. Genes Dev. (2003) [Pubmed]
  8. Inhibition of Wnt activity induces heart formation from posterior mesoderm. Marvin, M.J., Di Rocco, G., Gardiner, A., Bush, S.M., Lassar, A.B. Genes Dev. (2001) [Pubmed]
  9. Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer. Akahira, J.I., Aoki, M., Suzuki, T., Moriya, T., Niikura, H., Ito, K., Inoue, S., Okamura, K., Sasano, H., Yaegashi, N. Br. J. Cancer (2004) [Pubmed]
  10. Promoter analysis and chromosomal mapping of human EBAG9 gene. Ikeda, K., Sato, M., Tsutsumi, O., Tsuchiya, F., Tsuneizumi, M., Emi, M., Imoto, I., Inazawa, J., Muramatsu, M., Inoue, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  11. Reevaluation of the 22-1-1 antibody and its putative antigen, EBAG9/RCAS1, as a tumor marker. Reimer, T.A., Anagnostopoulos, I., Erdmann, B., Lehmann, I., Stein, H., Daniel, P., Dörken, B., Rehm, A. BMC Cancer (2005) [Pubmed]
  12. Molecular cloning and characterization of mouse EBAG9, homolog of a human cancer associated surface antigen: expression and regulation by estrogen. Tsuchiya, F., Ikeda, K., Tsutsumi, O., Hiroi, H., Momoeda, M., Taketani, Y., Muramatsu, M., Inoue, S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  13. Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells. Matsushima, T., Nakashima, M., Oshima, K., Abe, Y., Nishimura, J., Nawata, H., Watanabe, T., Muta, K. Blood (2001) [Pubmed]
  14. EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions. Suzuki, T., Inoue, S., Kawabata, W., Akahira, J., Moriya, T., Tsuchiya, F., Ogawa, S., Muramatsu, M., Sasano, H. Br. J. Cancer (2001) [Pubmed]
  15. A novel mechanism in suppression of erythropoiesis during inflammation: a crucial role of RCAS1. Suehiro, Y., Muta, K., Nakashima, M., Abe, Y., Shiratsuchi, M., Shiokawa, S., Ikuyama, S., Yoshikawa, Y., Watanabe, T., Nishimura, J. Eur. J. Haematol. (2005) [Pubmed]
  16. Expression of a tumor-associated antigen, RCAS1, in canine mammary tumors. Okamura, Y., Haraguchi, T., Morimoto, M., Okuda, M., Une, S., Nakaichi, M., Taura, Y. J. Vet. Med. Sci. (2004) [Pubmed]
  17. Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: diffuse down-regulation is associated with immune evasion and brain metastasis. Ohshima, K., Hamasaki, M., Makimoto, Y., Yoneda, S., Fujii, A., Takamatsu, Y., Nakashima, M., Watanabe, T., Kawahara, K., Kikuchi, M., Shirakusa, T. Int. J. Oncol. (2003) [Pubmed]
  18. Isolation of estrogen-responsive genes with a CpG island library. Watanabe, T., Inoue, S., Hiroi, H., Orimo, A., Kawashima, H., Muramatsu, M. Mol. Cell. Biol. (1998) [Pubmed]
  19. Protein and gene expression of tumor-associated antigen RCAS1 in esophageal squamous cell carcinoma. Ikeguchi, M., Ohoro, S., Maeda, Y., Yamaguchi, K., Fukuda, K., Shirai, H., Kondo, A., Tsujitani, S., Kaibara, N. Oncol. Rep. (2003) [Pubmed]
  20. The Role of RCAS1 and oxytocinase in immune tolerance during pregnancy. Wicherek, L., Dutsch-Wicherek, M., Mak, P., Klimek, M. Fetal. Diagn. Ther. (2005) [Pubmed]
  21. A clinical and immunohistochemical study on gastrointestinal mesenchymal tumor (GIMT): RCAS1 as a predictor for recurrence of GIMT. Naito, A., Narikiyo, M., Yamada, Y., Ueno, M., Kamada, K., Hachisuka, T., Yoriki, R., Mizuno, T., Nakajima, Y. Oncol. Rep. (2005) [Pubmed]
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