Disease relevance of VTCN1

• We show that B7-H4 mRNA and protein are overexpressed in human serous ovarian cancers and breast cancers with relatively little or no expression in normal tissues [1].
• Whereas overexpression of B7-H4 protected epithelial cells from anoikis, siRNA-mediated knockdown of B7-H4 mRNA and protein expression in a breast cancer cell line increased caspase activity and apoptosis [1].
• Overexpression of B7-H4 in a human ovarian cancer cell line with little endogenous B7-H4 expression increased tumor formation in SCID mice [1].
• B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival [2].
• We have developed a sensitive dual monoclonal antibody sandwich ELISA to analyze the level of B7-H4 protein in >2,500 serum samples, ascites fluids, and tissue lysates [3].

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

• B7-H4 protein is expressed on the surface of a variety of immune cells and functions as a negative regulator of T cell responses [1].
• The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation [1].
• Therefore, Treg cells convey suppressive activity to APCs by stimulating B7-H4 expression through IL-10 [6].
• B7-H4 staining intensity was greater in invasive ductal carcinomas [24.61 relative units (RU)] and in invasive lobular carcinomas (15.23 RU) than in normal breast epithelium (4.30 RU, P = 0.0003) [7].
• Low levels of B7-H4 expression were also detected in epithelial cells of the female genital tract, lung, pancreas, and kidney, but B7-H4 was generally absent in most other normal somatic tissues [7].

Associations of VTCN1 with chemical compounds

• EXPERIMENTAL DESIGN: Archival formalin-fixed tissue blocks from breast cancers and normal somatic tissues were evaluated for B7-H4 expression by immunohistochemistry with manual and automated image analysis [7].
• A 47 kDa fusion protein (GST/hB7-H4) was induced by isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified by standard methods reported in the prokaryotic system [8].

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].

References