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劳氏鼠白血病病毒诱导的红系、髓系和淋巴系细胞系中的癌基因表达。

Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines.

作者信息

de Both N J, van der Feltz M J, Mooren A, Vermaas D, Klaassen P, Rhijnsburger E H, Kranendonk-Odijk M E

机构信息

Department of Pathology, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.

出版信息

Leuk Res. 1989;13(1):53-64. doi: 10.1016/0145-2126(89)90031-3.

Abstract

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.

摘要

利用Northern印迹技术,对劳氏肉瘤病毒诱导的原发性白血病及其衍生的恶性程度更高的转化细胞系进行了核癌基因和细胞质癌基因表达的比较研究。后者可在体外永久生长。将从贫血恢复的小鼠获得的增生性脾脏作为对照进行分析。除了检测mRNA外,还进行了Southern印迹以观察癌基因是否发生重排或扩增。结果表明,核癌基因c-myc、c-myb和p53在白血病组织中强烈表达,而c-fos转录本的杂交信号则弱得多。在髓系白血病细胞分化过程中,对其中两个癌基因c-myc和c-myb的表达进行了跟踪,与组成型转录的肌动蛋白基因相比,其表达逐渐降低。白血病细胞系中表达了大量细胞质癌基因,即c-abl、c-fms、c-fes、c-src、c-ros、c-H-ras、c-K-ras和N-ras。其中,急性红白血病原始细胞中不存在编码c-abl和c-src的转录本。也未检测到编码c-erb、c-mos和c-sis的转录本。一些据报道在莫洛尼病毒和弗瑞德病毒诱导的白血病中起作用的假定癌基因,如pim-1、fis-1、fim-1和fim-2也用于筛选。仅在劳氏肉瘤病毒诱导的髓系白血病细胞和原发性急性红白血病中观察到pim-1的表达。在DNA水平上,未检测到所研究的任何癌基因发生重排或扩增。结果表明,多个癌基因在同一白血病组织或细胞系中同时表达。因此,不同癌基因转录本的存在似乎与白血病的进展有关,但不是白血病发生或这些细胞转化为成熟细胞系的主要原因。

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