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Gene Review

VTCN1  -  V-set domain containing T cell activation...

Homo sapiens

Synonyms: B7 homolog 4, B7-H4, B7H4, B7S1, B7X, ...
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Disease relevance of VTCN1


High impact information on VTCN1

  • Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies [2].
  • B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity [2].
  • High levels of B7-H4 protein were detected in ovarian cancer tissue lysates when compared with normal tissues [3].
  • Using cDNA database mining strategies and real-time quantitative reverse transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in ovarian and breast cancer tissues when compared with normal tissues [3].
  • The multivariate logistic regression analysis of B7-H4 and CA125 measured in the same sample set resulted in an area under the curve (AUC) of 0.86 for all stages and 0.86 for stage I/II patients, which was significantly higher than the AUC for either marker alone [3].

Biological context of VTCN1

  • The restricted normal tissue distribution of B7-H4, its overexpression in a majority of breast and ovarian cancers and functional activity in transformation validate this cell surface protein as a new target for therapeutic intervention [1].
  • B7-H4.Ig protein was purified from the culture supernatant of 293T cells transfected by a B7-H4.Ig plasmid (pMIgV, containing a human B7-H4 cDNA and a mouse IgG2a Fc cDNA) [4].
  • Mammaglobin 2, kallikreins 6, 7, 8, 10, 11, claudin 3 and 4 and B7-H4 gene expression products represent candidate biomarkers endowed with great potential for early screening and therapy of OSPC patients [5].

Anatomical context of VTCN1


Associations of VTCN1 with chemical compounds


Other interactions of VTCN1

  • The proportion of B7-H4-positive cells and the intensity of B7-H4 staining were compared with histologic type, grade, stage, hormone receptor status, and HER-2/neu status [7].
  • In vitro, mixed lymphocyte reactions revealed that TEC-related B7-H4 promotes cytokine (interleukin-2 and interferon-gamma) production and proliferation of co-cultured T cells [9].
  • Nevertheless, the expression and functional role of B7-H4, a recently identified co-stimulatory ligand of the B7 superfamily, in pathologic human kidneys is unclear [9].
  • Thirty-seven percent of the specimens expressed B7-H3 and 43% B7-H4 [10].
  • In this review, we will focus our discussion on two recently described molecules, B7-H1 and B7-H4, in the context of their roles in the evasion of tumor immunity and possible approaches for therapeutic manipulation [11].

Analytical, diagnostic and therapeutic context of VTCN1

  • Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses [2].
  • We investigated the expression of B7-H4 on cryostat renal biopsies from patients with idiopathic membranous nephropathy (n=20), immunoglobulin A nephropathy (n=19), lupus nephritis (n=16), and acute renal allograft rejection (n=15) using immunohistochemistry [9].
  • This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary [12].
  • Human islet cells express positive B7-H4 mRNA in RT-PCR assays, but not B7-H4 protein on cell surface in flow cytometric analyses [4].


  1. The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Salceda, S., Tang, T., Kmet, M., Munteanu, A., Ghosh, M., Macina, R., Liu, W., Pilkington, G., Papkoff, J. Exp. Cell Res. (2005) [Pubmed]
  2. B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Krambeck, A.E., Thompson, R.H., Dong, H., Lohse, C.M., Park, E.S., Kuntz, S.M., Leibovich, B.C., Blute, M.L., Cheville, J.C., Kwon, E.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Simon, I., Zhuo, S., Corral, L., Diamandis, E.P., Sarno, M.J., Wolfert, R.L., Kim, N.W. Cancer Res. (2006) [Pubmed]
  4. Suppression of human T-cell responses to beta-cells by activation of B7-H4 pathway. Ou, D., Wang, X., Metzger, D.L., Ao, Z., Pozzilli, P., James, R.F., Chen, L., Warnock, G.L. Cell transplantation. (2006) [Pubmed]
  5. Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: Identification of novel molecular biomarkers for early diagnosis and therapy. Bignotti, E., Tassi, R.A., Calza, S., Ravaggi, A., Romani, C., Rossi, E., Falchetti, M., Odicino, F.E., Pecorelli, S., Santin, A.D. Gynecol. Oncol. (2006) [Pubmed]
  6. Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. Kryczek, I., Wei, S., Zou, L., Zhu, G., Mottram, P., Xu, H., Chen, L., Zou, W. J. Immunol. (2006) [Pubmed]
  7. B7-h4 is highly expressed in ductal and lobular breast cancer. Tringler, B., Zhuo, S., Pilkington, G., Torkko, K.C., Singh, M., Lucia, M.S., Heinz, D.E., Papkoff, J., Shroyer, K.R. Clin. Cancer Res. (2005) [Pubmed]
  8. Recombinant human B7-H4 expressed in Escherichia coli inhibits T lymphocyte proliferation and IL-2 secretion in vitro. Mao, Y.X., Chen, Y.J., Ge, Y., Ma, H.B., Yu, J.F., Wu, H.Y., Hu, Y.M., Wang, Q., Shi, Q., Zhang, X.G. Acta Pharmacol. Sin. (2006) [Pubmed]
  9. Expression of the novel co-stimulatory molecule B7-H4 by renal tubular epithelial cells. Chen, Y., Yang, C., Xie, Z., Zou, L., Ruan, Z., Zhang, X., Tang, Y., Fei, L., Jia, Z., Wu, Y. Kidney Int. (2006) [Pubmed]
  10. B7-H3 and B7-H4 expression in non-small-cell lung cancer. Sun, Y., Wang, Y., Zhao, J., Gu, M., Giscombe, R., Lefvert, A.K., Wang, X. Lung Cancer (2006) [Pubmed]
  11. Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell immunity: novel cancer escaping mechanisms. Ichikawa, M., Chen, L. Front. Biosci. (2005) [Pubmed]
  12. B7-H4 overexpression in ovarian tumors. Tringler, B., Liu, W., Corral, L., Torkko, K.C., Enomoto, T., Davidson, S., Lucia, M.S., Heinz, D.E., Papkoff, J., Shroyer, K.R. Gynecol. Oncol. (2006) [Pubmed]
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