Pelicci P G, Lanfrancone L, Brathwaite M D, Wolman S R, Dalla-Favera R
Science. 1984 Jun 8;224(4653):1117-21. doi: 10.1126/science.6585957.
Amplification is one of the mechanisms by which cellular oncogenes may be altered in their function, possibly leading to neoplastic transformation. The oncogenes c-myc, c- abl , and c-Ki-ras are amplified in several different human neoplasias. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells, was found to be amplified in cell lines ML-1, ML-2, and ML-3, which were separately cultured from cells of a patient with acute myelogenous leukemia (AML). A five- to tenfold amplification was correlated with high levels of expression of normal size c-myb messenger RNA and with chromosomal abnormalities in the region 6q22 -24, where the c-myb locus is normally located. Amplification and cytogenetic abnormalities were detected in DNA's from primary and secondary cultures of ML cells, suggesting that they may have contributed to leukemogenesis. The similar AML cell lines HL-60 and ML's contain different amplified oncogenes: c-myc and c-myb, respectively. Alternative activation of structurally and possibly functionally similar oncogenes may distinguish--at the pathogenetic level--phenotypically similar tumors.
扩增是细胞癌基因功能可能发生改变的机制之一,可能导致肿瘤转化。癌基因c-myc、c-abl和c-Ki-ras在几种不同的人类肿瘤中发生扩增。在造血细胞中特异性表达和调控的癌基因c-myb,在分别从一名急性髓性白血病(AML)患者的细胞中培养得到的ML-1、ML-2和ML-3细胞系中被发现发生了扩增。5至10倍的扩增与正常大小的c-myb信使核糖核酸的高水平表达以及c-myb基因座正常所在的6q22 - 24区域的染色体异常相关。在ML细胞的原代和传代培养物的DNA中检测到扩增和细胞遗传学异常,表明它们可能对白血病发生有作用。类似的AML细胞系HL-60和ML分别含有不同的扩增癌基因:c-myc和c-myb。结构上可能功能也相似的癌基因的交替激活,在发病机制层面可能区分表型相似的肿瘤。