B7-H3 expression in breast cancer and upregulation of VEGF through gene silence.

B7-H3 expression in breast cancer and upregulation of VEGF through gene silence.
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乳腺癌中 B7-H3 的表达以及通过基因沉默上调 VEGF

DOI:
10.2147/ott.s63424
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发表时间:
2014
影响因子:
4
通讯作者:
Xiao Y
Xiao Y
中科院分区:
医学3区
文献类型:
--
作者:
Sun J;Guo YD;Li XN;Zhang YQ;Gu L;Wu PP;Bai GH;Xiao Y

文献摘要

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B7-H3是B7家族的新成员,以前被认为是调节T细胞介导的免疫反应的调节配体,近年来发现它在各种癌症中发挥重要作用。在某些肿瘤类型中,B7-H3的高表达与预后不良有关,而在其他癌症中观察到相反的效果。B7-H3在肿瘤免疫中的确切作用尚不清楚,需要进一步研究。在本研究中,我们研究了B7-H3的表达在221例乳腺癌患者的病理标本治疗免疫组化。B7-H3在80.55%的乳腺癌组织中呈强阳性表达,且与VEGF表达、CD 34微血管密度、肿瘤大小呈负相关。此外,通过脂多糖介导的稳定短发夹核糖核酸的递送,我们观察到B7-H3的沉默可以增加乳腺癌细胞系MCF-7中VEGF的转录和分泌。总之,本研究表明B7-H3通过抑制VEGF表达抑制肿瘤生长。这些结果增加了对B7-H3蛋白的非免疫学作用的认识,并为乳腺癌的重要生物学功能和假定的治疗靶点提供了新的见解。
B7-H3, a novel member of the B7 family, was previously known as a regulatory ligand regulating T-cell-mediated immune response, and in recent years it was found to take a significant role in various cancers. In some tumor types, high expression of B7-H3 had been linked to a poor prognosis, whereas in other cancers the opposite effect had been observed. The precise role of B7-H3 in tumor immunity is unclear, and further investigations are needed. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 221 patients treated for breast cancer by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 80.55% patients, and B7-H3 expression had a negative relation with vascular endothelial growth factor (VEGF) expression, microvascular density for CD34, and tumor size. Furthermore, through lipopolysaccharide-mediated delivery of stable short hairpin ribonucleic acid we observed that silencing of B7-H3 could increase the transcription and secreting of VEGF in breast cancer cell line MCF-7. In summary, the present study demonstrated that B7-H3 suppressed tumor growth through inhibiting VEGF expression. These results increased knowledge of the nonimmunological role of B7-H3 protein and provided novel insights into great biological functions and a putative therapeutic target in breast cancer.