BCSC-1 suppresses human breast cancer metastasis by inhibiting NF-B signaling
BCSC-1 suppresses human breast cancer metastasis by inhibiting NF-B signaling
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BCSC-1 通过抑制 NF-B 信号传导抑制人乳腺癌转移
DOI：
10.3892/ijo.2018.4309
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发表时间：
2018-05-01
影响因子：
5.2
通讯作者：
Ju, Jiyu
中科院分区：
文献类型：
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作者：
Di, Dalin;Chen, Lei;Ju, Jiyu
乳腺癌抑制候选基因 1（BCSC-1；也称为含有 5A 和 LOH11CR2A 的冯维勒布兰德因子 A 结构域）是一种新发现的候选肿瘤抑制基因，在之前的研究中已与多种类型的癌症有关。然而，近年来关于BCSC-1与人类乳腺癌关系的报道较少。在本研究中，通过组织微阵列和临床组织标本的免疫组织化学（IHC）染色测定乳腺癌中BCSC-1的表达。随后，通过定量聚合酶链式反应评估了不同乳腺癌细胞系中BCSC-1基因的表达，并选择MDA-MB-231细胞系因其BCSC-1表达较低而进一步用于后续实验。通过转染含BCSC-1基因的质粒，然后筛选G418抗性，建立稳定过表达BCSC-1的MDA-MB-231细胞系。进行伤口愈合、迁移和侵袭实验来检测BCSC-1对MDA-MB-231细胞的影响。此外，本研究还检测到基质金属蛋白酶 (MMP)、骨桥蛋白 (OPN) 和核因子 B (NF-B) 通路的变化。此外，使用慢病毒对 MCF-7 细胞中的 BCSC-1 表达进行稳定沉默。 IHC结果表明，与正常乳腺组织相比，乳腺癌组织中BCSC-1的表达水平较低。伤口愈合、迁移和侵袭实验结果表明，BCSC-1过表达降低了MDA-MB-231细胞的体外转移能力。进一步研究证实，BCSC-1过表达降低了MMP7、MMP9和OPN的表达水平，以及NF-B p65的磷酸化。此外，通过慢病毒介导的RNA干扰抑制BCSC-1表明BCSC-1的下调增加了MCF-7细胞的侵袭能力。总之，结果表明BCSC-1在乳腺癌组织中低水平表达，并且它可以抑制人乳腺癌细胞的迁移和侵袭，潜在地改变MMP7、MMP9、OPN的表达以及NF-B通路的活性。因此，BCSC-1可能在未来作为治疗乳腺癌的生物标志物。
Breast cancer suppressor candidate-1 (BCSC-1; also termed von Willebrand factor A domain containing 5A and LOH11CR2A) is a newly identified candidate tumor suppressor gene that has been implicated in several types of cancer in previous studies. However, there have been few reports about the association between BCSC-1 and human breast cancer in recent years. In the present study, the expression of BCSC-1 in breast cancer was determined by immunohistochemistry (IHC) staining of tissue microarrays and clinical tissue specimens. Subsequently, BCSC-1 gene expression was evaluated in different breast cancer cell lines by quantitative polymerase chain reaction and the MDA-MB-231 cell line was selected for further use in subsequent experiments, due to its low BCSC-1 expression. An MDA-MB-231 cell line with stable overexpression of BCSC-1 was established through transfection with plasmid containing the BCSC-1 gene, and then screening for G418 resistance. Wound-healing, migration and invasion assays were conducted to detect the effect of BCSC-1 on MDA-MB-231 cells. Furthermore, changes in matrix metalloproteinases (MMPs), osteopontin (OPN) and the nuclear factor-B (NF-B) pathway were detected in the current study. Additionally, stable silencing of BCSC-1 expression in MCF-7 cells was performed using a lentivirus. The results of IHC indicated that BCSC-1 is expressed at low levels in breast cancer tissues compared with in normal breast tissue. Results of the wound healing, migration and invasion assays demonstrated that BCSC-1 overexpression reduced the metastasis ability of MDA-MB-231 cells in vitro. Further research confirmed that the BCSC-1 overexpression reduced the expression levels of MMP7, MMP9 and OPN, and the phosphorylation of NF-B p65. Furthermore, inhibition of BCSC-1 via lentivirus-mediated RNA interference revealed that the downregulation of BCSC-1 increased the invasive ability of MCF-7 cells. In summary, the results demonstrated that BCSC-1 is expressed at low levels in breast cancer tissues, and that it can suppress human breast cancer cell migration and invasion, potentially altering the expression of MMP7, MMP9, OPN, and the activity of the NF-B pathway. Therefore, BCSC-1 may be useful as a biomarker for the treatment of breast cancer in the future.