Aberrant expression of BAFF receptor, a member of the tumor necrosis factor receptor family, in malignant cells of nonhematopoietic origins
Aberrant expression of BAFF receptor, a member of the tumor necrosis factor receptor family, in malignant cells of nonhematopoietic origins
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DOI：
10.1111/j.1365-2443.2008.01227.x
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发表时间：
2008-10
期刊：
影响因子：
2.1
通讯作者：
T. Kohno;T. Daa;H. Otani;I. Shimokawa;S. Yokoyama;T. Matsuyama
中科院分区：
文献类型：
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作者：
T. Kohno;T. Daa;H. Otani;I. Shimokawa;S. Yokoyama;T. Matsuyama
获得的逃避凋亡的能力是癌症发展的先决条件之一，NF-κB通过诱导抗凋亡分子起着关键作用。在这项研究中，我们首先进行了表达克隆的方法来分离NF-κB活化途径中的负责分子与缺陷突变细胞系COS-A717。与亲本COS细胞相比，该细胞系显示NF-κB的组成性基础活性降低。我们成功地分离出了对该途径具有补偿活性的基因，其中一个基因编码B-细胞活化因子受体（BAFF-R）。然而，北方印迹分析显示BAFF‐R表达不仅限于B细胞来源的细胞，而且在非造血来源的细胞中也发现。在人纤维肉瘤细胞系HT 1080中，免疫组织化学分析显示BAFF‐R的表达不在细胞表面，而是在细胞质中。同时检测到BAFF的表达，通过siRNA减少内源性BAFF或BAFF-R降低了基础NF-κB活性。最后，从临床病理标本中，BAFF-R和BAFF的相关表达在骨肉瘤中得到证实。我们认为，异常的BAFF/BAFF-R依赖性自分泌机制可能在某些类型的癌细胞的发展中发挥作用。
The acquired capability of evading apoptosis is one of the prerequisites for cancer development, and NF‐κB plays a critical role by inducing anti‐apoptotic molecules. In this study, we firstly carried out an expression‐cloning approach to isolate the responsible molecules in the NF‐κB activation pathway with the defective mutant cell line, COS‐A717. This cell line shows reduced constitutive basal activity of NF‐κB as compared with the parental COS cells. We successfully isolated genes with compensating activity for the pathway, and one gene encoded B‐cell activating factor receptor (BAFF‐R). However, a Northern blot analysis revealed that the BAFF‐R expression is not only limited to cells of B cell origin, but also is found in those with nonhematopoietic origins. In the human fibrosarcoma cell line HT1080, an immunohistochemical analysis revealed that the expression of BAFF‐R is not on the cell surface, but in the cytoplasm. The expression of BAFF was also detected, and the reduction of endogenous BAFF or BAFF‐R by siRNA decreased the basal NF‐κB activity. Lastly, from clinicopathological specimens, the associated expression of BAFF‐R and BAFF was demonstrated in osteosarcoma. We propose that an aberrant BAFF/BAFF‐R‐dependent autocrine mechanism may play a role in the development of certain types of cancer cells.