PAPILLOMAVIRUS SEQUENCES INTEGRATE NEAR CELLULAR ONCOGENES IN SOME CERVICAL CARCINOMAS
PAPILLOMAVIRUS SEQUENCES INTEGRATE NEAR CELLULAR ONCOGENES IN SOME CERVICAL CARCINOMAS
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DOI：
10.1073/pnas.84.4.1070
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发表时间：
1987-02-01
影响因子：
11.1
通讯作者：
HUEBNER, K
中科院分区：
文献类型：
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作者：
DURST, M;CROCE, CM;HUEBNER, K
在四个宫颈癌细胞系和一个原发性宫颈癌中，已确定了整合的乳头瘤病毒DNA侧翼细胞序列的染色体位置。来源于肿瘤的两个人乳头瘤病毒（HPV）16侧翼序列定位于染色体区域20 pter-20q13和3 p25-3qter，这两个区域还分别含有原癌基因c-src-1和c-raf-1。SiHa宫颈癌细胞系中的HPV 16整合位点位于染色体区域13 q14----13q32。SW 756宫颈癌细胞中的HPV 18整合位点位于12号染色体上，但与Ki-ras 2基因不紧密连锁。最后，在两种宫颈癌细胞系HeLa和C4-I中，HPV 18 DNA整合在c-myc基因的8号染色体5'端。HeLa HPV 18整合位点位于c-myc基因5'端的40个内切酶内，在围绕并包括c-myc基因的HL 60扩增单位内。此外，相对于其他宫颈癌细胞系，HeLa和C4-I细胞中c-myc mRNA的稳态水平升高。因此，至少在一些生殖器肿瘤中，HPV对细胞癌基因的顺式激活可能参与宫颈细胞的恶性转化。
The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical carcinoma cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosome regions 20pter----20q13 and 3p25----3qter, regions that also contain the protooncogenes c-src-1 and c-raf-1, respectively. The HPV 16 integration site in the SiHa cervical carcinoma-derived cell line is in chromosome region 13q14----13q32. The HPV 18 integration site in SW756 cervical carcinoma cells is in chromosome 12 but is not closely linked to the Ki-ras2 gene. Finally, in two cervical carcinoma cell lines, HeLa and C4-I, HPV 18 DNA is integrated in chromosome 8, 5' of the c-myc gene. The HeLa HPV 18 integration site is within 40 kilobases 5' of the c-myc gene, inside the HL60 amplification unit surrounding and including the c-myc gene. Additionally, steady-state levels of c-myc mRNA are elevated in HeLa and C4-I cells relative to other cervical carcinoma cell lines. Thus, in at least some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells.