B7-H4 Expression Promotes Tumorigenesis in Ovarian Cancer

B7-H4 Expression Promotes Tumorigenesis in Ovarian Cancer
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DOI:
10.1111/igc.0b013e3181ad0fa2
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发表时间:
2009-12-01
影响因子:
4.8
通讯作者:
Kong, Beihua
Kong, Beihua
中科院分区:
医学3区
文献类型:
--
作者:
Cheng, Lei;Jiang, Jie;Kong, Beihua

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简介:先前已经显示,B7-H4(B7家族成员之一,充当T细胞功能的负调节剂)在多种癌症中具有改变的表达水平,B7-H4的过表达促进细胞转化。方法:构建pE-green fluorescent protein-N1/B7-H4真核表达载体,转染B7-H4阴性的人卵巢癌细胞株SKOV 3。在体外检测细胞增殖、凋亡、粘附、运动和侵袭。结果:荧光显微镜观察证实,B7-H4-绿色荧光蛋白定位于SKOV 3/B7-H4细胞的胞浆内,而绿色荧光蛋白则均匀分布于整个细胞内。B7-H4促进细胞增殖,增加细胞粘附、迁移和侵袭。结论:B7-H4可直接促进卵巢癌细胞的恶性转化,为靶向B7-H4抑制卵巢癌的发展提供了一种潜在的治疗策略。
Introduction: It has been previously shown that B7-H4, one of the B7 family members that serve as negative regulators of T cell function, has altered expression levels in a variety of cancers, overexpression of B7-H4 promotes cellular transformation. However, there is still lack of adequate evidence to establish a direct connection between B7-H4 expression and malignant transformation.Methods: Herein, we constructed pE-green fluorescent protein-N1/B7-H4 mammalian expression vector and transfected into B7-H4-negative human ovarian cancer cell line SKOV3. Cellular proliferation, apoptosis, adhesion, motility, and invasion were examined in vitro. Cells injected subcutaneously into severe combined immunodeficient mouse were analyzed for the possible functions of B7-H4 in ovarian tumorigenesis in vivo.Results: Fluorescence microscopy Studies confirmed that the B7-H4-green fluorescent protein localizes in the cytoplasm of SKOV3/B7-H4 cells, whereas green fluorescent protein is uniformly distributed throughout the cell. B7-H4 promoted cellular proliferation rate and increased cell adhesion, migration, and invasion. In addition, SKOV3 cells expressing B7-H4 gained growth advantage in the xenograft model in vivo.Conclusions: These studies demonstrate that B7-H4 directly promotes malignant transformation of ovarian cancer cell line, and provides a potential therapeutic strategy for targeting B7-H4 to inhibit progression of human ovarian cancers.