IDENTIFICATION OF HUMAN PAPILLOMAVIRUS TYPE-18 TRANSFORMING GENES IN IMMORTALIZED AND PRIMARY-CELLS

IDENTIFICATION OF HUMAN PAPILLOMAVIRUS TYPE-18 TRANSFORMING GENES IN IMMORTALIZED AND PRIMARY-CELLS
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DOI:
10.1128/jvi.63.3.1247-1255.1989
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发表时间:
1989-03-01
影响因子:
5.4
通讯作者:
LAIMINS, LA
LAIMINS, LA
中科院分区:
医学2区
文献类型:
--
作者:
BEDELL, MA;JONES, KH;LAIMINS, LA

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宫颈癌中人乳头瘤病毒(HPV)16型和18型E6-E7区的选择性保留和表达表明,这些病毒序列在生殖器肿瘤的发展中发挥作用。三种可能的基因产物,E6,E6*,和E7,从HPV-18的这个区域的每一个进行了检查,在几种类型的啮齿动物细胞的转化特性。我们已经发现,在永生化的成纤维细胞中,E6和E7(但不是E6*)都能够诱导锚定非依赖性生长。在大鼠胚胎细胞中,HPV-18 E7开放阅读框架是一种有效的永生化试剂,并补充了激活的ras癌基因进行转化。在永生化和原代细胞中,当HPV-18序列从HPV-18启动子或异源启动子表达时,观察到转化。然而,E6-E7区域不是HPV-18的唯一转化结构域,因为早期区域的另一部分,可能是E5,也在永生化成纤维细胞中表现出转化能力。因此,人类宫颈癌的发展可能涉及一系列涉及多种病毒和细胞基因产物的步骤。
The selective retention and expression of the E6-E7 region of human papillomavirus (HPV) types 16 and 18 in cervical carcinomas suggests that these viral sequences play a role in the development of genital neoplasia. Each of three possible gene products, E6, E6*, and E7, from this region of HPV-18 were examined for transforming properties in several types of rodent cells. We have found that in immortalized fibroblasts, both E6 and E7 (but not E6*) are capable of inducing anchorage-independent growth. In rat embryo cells, the HPV-18 E7 open reading frame was an effective immortalizing agent and complemented an activated ras oncogene for transformation. In both immortalized and primary cells, transformation was observed when the HPV-18 sequences were expressed from either the HPV-18 promoter or a heterologous promoter. The E6-E7 region is not, however, the sole transforming domain of HPV-18, since another portion of the early region, possibly E5, also exhibited transforming capability in immortalized fibroblasts. The development of human cervical carcinomas may therefore involve a series of steps involving multiple viral and cellular gene products.