Dobner T, Wolf I, Emrich T, Lipp M
Institut für Biochemie, Ludwig-Maximilians-Universität, Munich, FRG.
Eur J Immunol. 1992 Nov;22(11):2795-9. doi: 10.1002/eji.1830221107.
Deregulation of the proto-oncogene MYC by specific chromosomal translocations has been shown to be essential but not sufficient for the development of Burkitt's lymphoma (BL). To identify other genes which either mark important steps in tumorigenesis or which reflect the cellular differentiation state of BL cells we have compared tumor cells to immortalized lymphoblastoid B cells by subtractive hybridization. We have identified a complementary DNA clone which encodes a novel member of the superfamily of GTP-binding (G) protein-coupled receptors, designated BLR1. The corresponding mRNA is expressed in BL and lymphatic tissues but not in other cell lines either of the B cell lineage or of other hematopoietic or non-hematopoietic origin. This exclusive expression of BLR1 and the oncogenic potential of this receptor class supports the hypothesis that BLR1 exerts a regulatory function in BL lymphomagenesis and/or B cell differentiation. Moreover, the protein sequence is highly related to that of receptors for the cytokine interleukin (IL)-8 and other neutrophil chemoattractants. We conclude that BLR1 may represent a potential candidate involved in the process of physiologic trafficking, cell-cell interactions, and activation of mature B lymphocytes in lymphatic tissues.
特定染色体易位导致的原癌基因MYC失调已被证明是伯基特淋巴瘤(BL)发生所必需的,但并不充分。为了鉴定在肿瘤发生过程中标志重要步骤或反映BL细胞分化状态的其他基因,我们通过消减杂交将肿瘤细胞与永生化淋巴母细胞样B细胞进行了比较。我们鉴定出一个互补DNA克隆,它编码一种GTP结合(G)蛋白偶联受体超家族的新成员,命名为BLR1。相应的mRNA在BL和淋巴组织中表达,但在B细胞系或其他造血或非造血来源的其他细胞系中不表达。BLR1的这种特异性表达以及该受体类别的致癌潜力支持了这样的假设,即BLR1在BL淋巴瘤发生和/或B细胞分化中发挥调节功能。此外,蛋白质序列与细胞因子白细胞介素(IL)-8和其他中性粒细胞趋化因子的受体高度相关。我们得出结论,BLR1可能是参与淋巴组织中生理运输、细胞间相互作用以及成熟B淋巴细胞激活过程的潜在候选者。