Newman J D, Harrison L C
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Int J Cancer. 1989 Sep 15;44(3):467-73. doi: 10.1002/ijc.2910440315.
The specific binding of insulin to 7 different Burkitt lymphoma cell lines containing chromosomal translocations t(8;14), t(8;2) and t(8;22) was markedly decreased when compared to binding to lymphoblastoid cells of normal karyotype derived from Burkitt lymphoma patients or the human IM-9 lymphoblastoid line. The number of insulin-binding sites on intact Burkitt cells was decreased by greater than 90% compared to lymphoblastoid cells, with no change in affinity. This decrease in binding was paralleled by reduced amounts of insulin receptor alpha (Mr 130,000) and beta (Mr 95,000) subunits detected by cell-surface-labelling and insulin receptor mRNA transcripts, indicating that transcription of receptor mRNA is decreased in Burkitt cells compared to lymphoblastoid cells and/or that receptor mRNA is less stable. Burkitt cells displayed negligible insulin-stimulated beta subunit auto-phosphorylation, which could reflect either their decreased number of receptors or a defect in signal transduction. Structural analysis also revealed that the Burkitt cells had an increase in a precursor form (Mr 210,000) of the receptor, suggesting that decreased expression of the receptor may be associated with defective processing. Four Burkitt cell lines with t(8;14) also had reductions of 45-100% in expression of class-1 major histocompatibility (MHC) antigens. The expression of insulin receptors in both Burkitt and lymphoblastoid cells correlated with the expression of class-1 MHC antigens. There was also an inverse correlation between the expression of c-myc and both insulin receptors and class-1 MHC antigens. As the insulin receptor is absent on resting B cells and is induced after cell activation, the decrease in receptor expression on Burkitt cells may reflect their less activated phenotype compared to lymphoblastoid cells.
与胰岛素与源自伯基特淋巴瘤患者的正常核型淋巴母细胞或人IM-9淋巴母细胞系的结合相比，胰岛素与7种不同的含有染色体易位t(8;14)、t(8;2)和t(8;22)的伯基特淋巴瘤细胞系的特异性结合明显降低。与淋巴母细胞相比，完整伯基特细胞上胰岛素结合位点的数量减少了90%以上，亲和力没有变化。这种结合的减少与通过细胞表面标记和胰岛素受体mRNA转录本检测到的胰岛素受体α（分子量130,000）和β（分子量95,000）亚基数量的减少平行，表明与淋巴母细胞相比，伯基特细胞中受体mRNA的转录减少和/或受体mRNA不太稳定。伯基特细胞显示出可忽略不计的胰岛素刺激的β亚基自磷酸化，这可能反映了它们受体数量的减少或信号转导缺陷。结构分析还显示，伯基特细胞中受体的前体形式（分子量210,000）增加，表明受体表达的降低可能与加工缺陷有关。4种具有t(8;14)的伯基特细胞系中，1类主要组织相容性（MHC）抗原的表达也降低了45%-100%。伯基特细胞和淋巴母细胞中胰岛素受体的表达与1类MHC抗原的表达相关。c-myc的表达与胰岛素受体和1类MHC抗原的表达之间也呈负相关。由于静息B细胞上不存在胰岛素受体，且在细胞活化后被诱导，伯基特细胞上受体表达的降低可能反映了它们与淋巴母细胞相比活化表型较弱。
