The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation

被引：282

作者：

Salceda, S ^{[1
]}

Tang, T ^{[1
]}

Kmet, M ^{[1
]}

Munteanu, A ^{[1
]}

Ghosh, M ^{[1
]}

Macina, R ^{[1
]}

Liu, WH ^{[1
]}

Pilkington, G ^{[1
]}

Papkoff, J ^{[1
]}

机构：

[1] DiaDexus Inc, San Francisco, CA 94080 USA

来源：

EXPERIMENTAL CELL RESEARCH | 2005年 / 306卷 / 01期

关键词：

B7-H4; B7x; ovarian cancer; breast cancer; apoptosis;

D O I：

10.1016/j.yexcr.2005.01.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

B7-H4 protein is expressed on the surface of a variety of immune cells and functions as a negative regulator of T cell responses. We independently identified B7-H4 (DD-O110) through a genomic effort to discover genes upregulated in tumors and here we describe a new functional role for B7-H4 protein in cancer. 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. B7-H4 protein is extensively glycosylated and displayed on the surface of tumor cells and we provide the first demonstration of a direct role for B7-H4 in promoting malignant transformation of epithelial cells. Overexpression of B7-H4 in a human ovarian cancer cell line with little endogenous B7-H4 expression increased tumor formation in SCID mice. 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. 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. A therapeutic antibody strategy aimed at B7-H4 could offer an exciting opportunity to inhibit the growth and progression of human ovarian and breast cancers. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：128 / 141

页数：14

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