Shinozawa I, Inokuchi K, Wakabayashi I, Dan K
Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Leuk Res. 2000 Nov;24(11):965-70. doi: 10.1016/s0145-2126(00)00065-5.
Survivin is a newly discovered inhibitor of the apoptosis protein, IAP, expressed during development and in human cancers. The effector cell protease receptor-1 (EPR-1) gene is oriented in the opposite direction on the same DNA double strand. Thus, the Survivin and EPR-1 (Survivin/EPR-1) genes exist in a head-to-head configuration. It is not clear whether mutual expression of the Survivin/EPR-1 genes occurs in both normal cells and cancer cells. Here, we investigated the mutual expression of the Survivin/EPR-1 genes in 12 normal peripheral blood (PB) specimens, seven normal bone marrow (BM) specimens, five lymph node (LN) specimens, and seven leukemic cell lines, and 27 patients with malignant lymphoma (ML), four with acute lymphocytic leukemia (ALL), three with acute myelocytic leukemia (AML), and four with chronic myelocytic leukemia in blastic crisis (CML-BC). Using Northern blot analysis, small amounts of EPR-1 mRNA were detected in normal PB, normal BM and LN specimens, but no Survivin mRNA was detected. However, Survivin mRNA was detected in two of the 12 normal PB, six of the seven normal BM and one of the five LN specimens using reverse transcription and polymerase chain reaction (RT-PCR). Expression of both the Survivin and EPR-1 genes was detected in six of the seven cell line samples by Northern blot, and in all of them by RT-PCR. Mutual expression of the Survivin and EPR-1 genes was detected in three of the four CML-BC samples, 15 of the 27 ML samples, two of the four ALL samples, and all three AML samples using the RT-PCR method. No EPR-1 expression with or without Survivin expression was clearly detected in eight of the nine diffuse large B-cell lymphoma (DLB) specimens, two of the six follicular center lymphoma specimens, one of the four specimens of nodular sclerosis of Hodgkin's lymphoma, two of the four ALL specimens or one of the four CML-BC specimens. The data presented here show that disrupted expression of the Survivin/EPR-1 genes occurred in many kinds of hematologically malignant cells. This may be of biological importance.
生存素是一种新发现的凋亡蛋白抑制因子，属于IAP家族，在发育过程及人类癌症中均有表达。效应细胞蛋白酶受体-1（EPR-1）基因在同一条DNA双链上呈相反方向排列。因此，生存素和EPR-1（Survivin/EPR-1）基因以头对头的形式存在。目前尚不清楚Survivin/EPR-1基因在正常细胞和癌细胞中是否相互表达。在此，我们研究了Survivin/EPR-1基因在12份正常外周血（PB）标本、7份正常骨髓（BM）标本、5份淋巴结（LN）标本、7株白血病细胞系，以及27例恶性淋巴瘤（ML）患者、4例急性淋巴细胞白血病（ALL）患者、3例急性髓细胞白血病（AML）患者和4例慢性髓细胞白血病急变期（CML-BC）患者中的相互表达情况。通过Northern印迹分析，在正常PB、正常BM和LN标本中检测到少量EPR-1 mRNA，但未检测到生存素mRNA。然而，使用逆转录聚合酶链反应（RT-PCR）在12份正常PB标本中的2份、7份正常BM标本中的6份和5份LN标本中的1份中检测到了生存素mRNA。通过Northern印迹在7株细胞系样本中的6份中检测到了Survivin和EPR-1基因的表达，通过RT-PCR在所有样本中均检测到了表达。使用RT-PCR方法在4份CML-BC样本中的3份、27份ML样本中的15份、4份ALL样本中的2份和所有3份AML样本中检测到了Survivin和EPR-1基因的相互表达。在9份弥漫性大B细胞淋巴瘤（DLB）标本中的8份、6份滤泡中心淋巴瘤标本中的2份、4份霍奇金淋巴瘤结节硬化标本中的1份、4份ALL标本中的2份或4份CML-BC标本中的1份中，无论有无生存素表达，均未明确检测到EPR-1表达。此处呈现的数据表明，Survivin/EPR-1基因的表达紊乱发生在多种血液系统恶性细胞中。这可能具有生物学重要性。
