Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer

Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer
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DOI:
10.1097/00029330-200710020-00007
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发表时间:
2007-10-20
影响因子:
6.1
通讯作者:
Wang Shen-Ming
Wang Shen-Ming
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Yao;Ying, Lin;Wang Shen-Ming

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研究背景雌激素受体(ER)是乳腺癌的重要生物标志物。ER缺失与肿瘤的进展、复发、转移及预后不良有关,但其生物学机制尚不清楚。ER阴性乳腺癌表达高水平的白细胞介素-8(IL-8)。ER表达可下调IL-8启动子活性。IL-8作为一种多功能细胞因子,在肿瘤的发生、发展中具有重要的生物学活性。为探讨IL-8在ER阴性乳腺癌发生发展中的作用,我们应用RNA干扰技术特异性地敲低ER阴性乳腺癌细胞株MDA-MB-231中IL-8的表达。观察转染、未转染和阴性转染细胞的增殖、凋亡和侵袭能力。结果IL-8的表达降低与细胞侵袭能力降低有关(P0. 05)。在体内实验中,pRNA-IL-8转染的细胞与未转染和阴性转染的细胞相比,中性粒细胞浸润明显受到抑制(P=0.001,P
Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interleukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.Methods Interfering pRNA-IL-8 and the control was transfected into ER(-) MDA-MB-231. The proliferation, cell apotosis, and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).Results In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P=0.001, P