Oncogene expression in autoimmune and normal peripheral blood mononuclear cells.

Oncogene expression in autoimmune and normal peripheral blood mononuclear cells.
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DOI:
10.1084/jem.163.5.1292
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发表时间:
1986-05-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Steinberg AD
Steinberg AD
中科院分区:
其他
文献类型:
--
作者:
Klinman DM;Mushinski JF;Honda M;Ishigatsubo Y;Mountz JD;Raveche ES;Steinberg AD

文献摘要

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研究了来自自身免疫性疾病患者和正常对照的 PBMC 的几种细胞癌基因的表达。通过对从白细胞分离样本中获得的 Poly(A)+ RNA 进行 Northern 印迹分析来评估基因表达。 SLE 患者表达的 c-myc 原癌基因 RNA 明显高于正常对照。在自身免疫性疾病非常活跃的患者亚群中发现 N-ras 原癌基因表达增加。来自系统性红斑狼疮患者(而非其他自身免疫性疾病患者)的细胞显示 c-myb 和 c-fos 原癌基因水平显着降低。为了检验这些发现的意义,从正常志愿者捐赠的单采血液样本中纯化了 B 细胞和 T 细胞。当使用有丝分裂原在体外激活 B 细胞时,它们的原癌基因表达模式发生变化,类似于从狼疮患者中新鲜分离的细胞中发现的模式。这些结果表明,SLE患者原癌基因表达的差异可能是由于体内B细胞的异常激活所致。在患有其他自身免疫性疾病的患者中发现的原癌基因表达模式与这些疾病中其他细胞类型的激活一致。
PBMC from patients with autoimmune diseases and from normal controls were studied for the expression of several cellular oncogenes. Gene expression was assessed by Northern blot analysis of poly(A)+ RNA obtained from leukapheresis samples. Patients with SLE expressed significantly more c-myc protooncogene RNA than did normal controls. Increased expression of the N-ras protooncogene was found in that subset of patients whose autoimmune disease was very active. Cells from individuals with SLE, but not from those with other autoimmune illnesses, showed significantly decreased levels of the c-myb and c-fos protooncogenes. To examine the implications of these findings, B and T cells were purified from apheresis samples donated by normal volunteers. When mitogen was used to activate the B cells in vitro, their pattern of protooncogene expression changed to resemble that found in freshly isolated cells from lupus patients. These results suggest that the differences detected in the expression of protooncogenes by patients with SLE may be due to the abnormal activation of their B cells in vivo. The pattern of protooncogene expression found in patients with other autoimmune illnesses is consistent with the activation of additional cell types in those diseases.