AMPLIFICATION OF ENDOGENOUS MYC-RELATED DNA-SEQUENCES IN A HUMAN MYELOID-LEUKEMIA CELL-LINE

AMPLIFICATION OF ENDOGENOUS MYC-RELATED DNA-SEQUENCES IN A HUMAN MYELOID-LEUKEMIA CELL-LINE
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DOI:
10.1038/298679a0
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发表时间:
1982-01-01
期刊:
影响因子:
64.8
通讯作者:
GROUDINE, M
GROUDINE, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
COLLINS, S;GROUDINE, M

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急性转化RNA肿瘤病毒引起的细胞恶性转化是由某些特定的前病毒DNA序列(“癌基因”)的表达介导的。这些序列已被很好地表征,并且在许多情况下,分子克隆1 -8。这些病毒致癌基因与正常未感染细胞中发现的类似基因相关9,10。此外,这些特定的序列在进化中是高度保守的4,11,这表明这些基因在正常细胞功能中具有重要的,尽管未知的作用。有人认为,增加剂量的产品,这种内源性致癌基因可能是负责恶性转化10,12,13。例如,在禽白血病病毒诱导的鸡法氏囊淋巴细胞转化中观察到内源性鸡c-myconcogene的表达增加12。在这里,我们表明,在正常的人类DNA中的同源序列的禽流感基因存在于多个拷贝的人类白血病细胞系HL-60的染色体DNA。来自Abelson白血病病毒4和猫肉瘤病毒6的其他转化特异性基因在HL-60中未扩增。在其他培养的人髓性白血病细胞(包括K-56214和KG-115)中不存在Thismyc-related基因扩增。
Malignant transformation of cells by acute transforming RNA tumour viruses is mediated by the expression of certain specific pro viral DNA sequences (‘oncogenes’). These sequences have been well characterized and, in many cases, molecularly cloned1–8. These viral oncogenes are related to similar genes found in normal uninfected cells9,10. Moreover, these particular sequences are highly conserved in evolution4,11, suggesting that these genes have an important, albeit unknown, role in normal cell function. It has been suggested that an increased dosage of products of such endogenous oncogenes may be responsible for malignant transformation10,12,13. For example, increased expression of the endogenous chick c-myconcogene has been observed in avian leukosis virus-induced transformation of chick bursal lymphocytes12. Here we demonstrate that sequences in normal human DNA homologous to the avianmyconcogene are present in multiple copies in the chromosomal DNA of the human leukaemia cell line HL-60. Other transformation-specific genes derived from the Abelson leukaemia virus4and feline sarcoma virus6are not amplified in HL-60. Thismyc-related gene amplification is not present in other cultured human myeloid leukaemia cells, including K-56214and KG-115.