Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis.
Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis.
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DOI：
10.1186/1471-2407-9-102
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发表时间：
2009-04-01
期刊：
影响因子：
3.8
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Cai D;Cao J;Li Z;Zheng X;Yao Y;Li W;Yuan Z
骨转移是乳腺癌常见的并发症。最近的文献表明多种趋化因子参与了乳腺癌骨转移的形成。然而，乳腺癌骨转移的分子机制仍不清楚。最近，我们在人乳腺癌细胞系中发现了BST 2蛋白的表达。本研究旨在探讨BST 2在骨转移性乳腺癌中的表达及其作用。用cDNA微阵列分析比较骨转移性人乳腺癌细胞系（MDA-231 BO）和原代人乳腺癌细胞系（MDA-231）之间BST 2基因表达。还使用实时RT-PCR和蛋白质印迹法测定了一种骨转移性乳腺癌和七种非骨转移性乳腺癌细胞系中BST 2的表达。然后，我们采用组织阵列进一步研究BST 2在人乳腺癌中的表达，使用含有20个形成转移性骨病变的独立乳腺癌肿瘤、30个非转移形成乳腺癌肿瘤和8个正常乳腺组织的阵列载玻片。为了测试利用BST 2作为乳腺癌中骨转移存在的血清标志物的可行性，我们通过使用ELISA测量了43名有骨转移的乳腺癌患者、43名无骨转移的乳腺癌患者和14名正常健康对照者的人血清中BST 2的表达水平。还使用迁移和FACS分析在人乳腺重组模型系统中研究了细胞迁移和增殖与BST 2表达之间的关系。微阵列显示，与原代人乳腺癌细胞系（MDA-231）相比，骨转移性乳腺癌细胞系（MDA-231 BO）中BST 2基因的过表达。通过真实的时间RT-PCR、Western blot和TMA检测，BST 2基因在骨转移乳腺癌细胞系和肿瘤组织中的表达均显著高于非骨转移乳腺癌细胞系和肿瘤组织。此外，与未转移到骨的乳腺癌患者相比，转移到骨的乳腺癌患者中通过ELISA测量的血清BST 2水平也显著更高（P < .0001）。最重要的是，用BST 2转染的乳腺癌细胞系表现出增加的BST 2表达，这与增加的癌细胞迁移和细胞增殖有关。这些结果提供了新的数据，表明BST 2蛋白表达与人乳腺癌骨转移的形成有关。我们认为，BST 2可能是乳腺癌骨转移的潜在生物标志物。
Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer cell lines and tumor tissues by real time RT-PCR, Western blot and TMA. Furthermore, serum levels of BST2 measured by ELISA were also significantly higher among patients with breast cancer metastatic to bone compared to breast cancer patients without metastatic to bone (P < .0001). Most importantly, the breast cancer cell line that transfected with BST2 demonstrated increased BST2 expressions, which was associated with increased cancer cell migration and cell proliferation. These results provide novel data indicating the BST2 protein expression is associated with the formation of bone metastases in human breast cancer. We believe that BST2 may be a potential biomarker in breast cancer with bone metastasis.
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DOI：
10.1006/bbrc.1999.0683
发表时间：
1999-05-19
影响因子：
3.1
作者：
Ohtomo, T;Sugamata, Y;Tsuchiya, M
通讯作者：
Tsuchiya, M
影响因子：
6.4
作者：
Salgado, R;Junius, S;Dirix, LY
通讯作者：
Dirix, LY
影响因子：
64.5
作者：
Bromberg, JF;Wrzeszczynska, MH;Darnell, JE
通讯作者：
Darnell, JE
影响因子：
8
作者：
Yuan, ZQ;Gaba, AG;Weber, TK
通讯作者：
Weber, TK
影响因子：
6.2
作者：
Yoneda, T;Williams, PJ;Nishimura, R
通讯作者：
Nishimura, R