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用人乳头瘤病毒16型DNA和EJ-ras对原代人成纤维细胞进行转化。

Transformation of primary human fibroblast cells with human papillomavirus type 16 DNA and EJ-ras.

作者信息

Matlashewski G, Osborn K, Banks L, Stanley M, Crawford L

机构信息

Institute of Parasitology, McGill University, Macdonald College, Ste.-Anne-de-Bellevue, Quebec, Canada.

出版信息

Int J Cancer. 1988 Aug 15;42(2):232-8. doi: 10.1002/ijc.2910420215.

DOI:10.1002/ijc.2910420215
PMID:2841248
Abstract

Human papillomavirus type 16 (HPV type 16) has been implicated as an etiological agent in human cervical cancer. This virus contains sequences which, under the proper transcriptional control, can increase the tumorigenicity of established mouse cells and cooperate with EJ-ras in transforming primary baby rat kidney (BRK) cells. These data argue that this virus contains oncogenic sequences. Because this is a human virus, it was important to study the effect on primary human cells of HPV type-16 DNA in both the presence and absence of EJ-ras. We now present data which demonstrate that HPV type-16 DNA, under the transcriptional control of Moloney murine leukemia viral long terminal repeats (MoMuLV-LTR), can extend the life span of primary human fibroblast cells in culture. Co-transfection of the HPV type-16 DNA containing plasmid together with an activated EJ-ras oncogene gives rise to transformed cells which grow faster, are morphologically different from and more aneuploid than cells established with only HPV type-16 DNA. Molecular analysis of these established and partially transformed human cells reveals that they contain and express the transfected DNA. These data argue that primary human cells can be transformed with HPV type-16 and EJ-ras sequences, whereas cells harboring only HPV type 16 DNA are largely normal but have an extended life span.

摘要

16型人乳头瘤病毒(HPV-16)被认为是人类宫颈癌的病原体。该病毒包含一些序列,在适当的转录控制下,这些序列可增加已建立的小鼠细胞的致瘤性,并在转化原代新生大鼠肾(BRK)细胞中与EJ-ras协同作用。这些数据表明该病毒含有致癌序列。由于这是一种人类病毒,因此研究有无EJ-ras时HPV-16 DNA对原代人类细胞的影响非常重要。我们现在展示的数据表明,在莫洛尼鼠白血病病毒长末端重复序列(MoMuLV-LTR)的转录控制下,HPV-16 DNA可延长培养中原代人成纤维细胞的寿命。将含有HPV-16 DNA的质粒与激活的EJ-ras癌基因共转染可产生转化细胞,这些细胞生长更快,在形态上与仅用HPV-16 DNA建立的细胞不同,且非整倍性更高。对这些已建立并部分转化的人类细胞的分子分析表明,它们含有并表达转染的DNA。这些数据表明,原代人类细胞可被HPV-16和EJ-ras序列转化,而仅含有HPV-16 DNA的细胞基本正常,但寿命延长。

相似文献

1
Transformation of primary human fibroblast cells with human papillomavirus type 16 DNA and EJ-ras.用人乳头瘤病毒16型DNA和EJ-ras对原代人成纤维细胞进行转化。
Int J Cancer. 1988 Aug 15;42(2):232-8. doi: 10.1002/ijc.2910420215.
2
Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells.16型人乳头瘤病毒DNA与激活的ras协同作用转化原代细胞。
EMBO J. 1987 Jun;6(6):1741-6. doi: 10.1002/j.1460-2075.1987.tb02426.x.
3
Transformation of primary BRK cells by human papillomavirus type 16 and EJ-ras is increased by overexpression of the viral E2 protein.人乳头瘤病毒16型和EJ - ras对原代BRK细胞的转化作用会因病毒E2蛋白的过表达而增强。
J Gen Virol. 1990 Jan;71 ( Pt 1):183-93. doi: 10.1099/0022-1317-71-1-183.
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Proc Natl Acad Sci U S A. 1988 Dec;85(23):8820-4. doi: 10.1073/pnas.85.23.8820.
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Glucocorticoid-dependent oncogenic transformation by type 16 but not type 11 human papilloma virus DNA.16型而非11型人乳头瘤病毒DNA介导的糖皮质激素依赖性致癌转化
Nature. 1988 Oct 27;335(6193):832-5. doi: 10.1038/335832a0.
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[The possibility of viral etiology in cervical carcinogenesis].[宫颈癌发生中病毒病因的可能性]
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Cell lines containing and expressing the human herpesvirus 6A ts gene are protected from both H-ras and BPV-1 transformation.含有并表达人疱疹病毒6A温度敏感基因的细胞系对H-ras和BPV-1转化均具有抗性。
Oncogene. 1997 Feb 27;14(8):937-43. doi: 10.1038/sj.onc.1200899.
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Continued expression of HPV-16 E7 protein is required for maintenance of the transformed phenotype of cells co-transformed by HPV-16 plus EJ-ras.HPV-16 E7蛋白的持续表达是维持由HPV-16与EJ-ras共同转化的细胞的转化表型所必需的。
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Human papillomavirus types 6 and 16 in cooperation with Ha-ras transform secondary rat embryo fibroblasts.人乳头瘤病毒6型和16型与Ha-ras协同作用可转化二代大鼠胚胎成纤维细胞。
J Gen Virol. 1989 Feb;70 ( Pt 2):353-65. doi: 10.1099/0022-1317-70-2-353.

引用本文的文献

1
Persistence of high-grade cervical dysplasia and cervical cancer requires the continuous expression of the human papillomavirus type 16 E7 oncogene.高级别宫颈发育异常和宫颈癌的持续存在需要人乳头瘤病毒16型E7癌基因的持续表达。
Cancer Res. 2009 May 15;69(10):4407-14. doi: 10.1158/0008-5472.CAN-09-0023. Epub 2009 May 12.
2
Molecular events in uterine cervical cancer.子宫颈癌中的分子事件
Sex Transm Infect. 1998 Apr;74(2):101-9. doi: 10.1136/sti.74.2.101.
3
Human papillomavirus, integration and cervical carcinogenesis: a clinicopathological perspective.
人乳头瘤病毒、整合与宫颈癌发生:临床病理学视角
Mol Pathol. 1997 Feb;50(1):1-3. doi: 10.1136/mp.50.1.1.
4
Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis.人乳头瘤病毒16型DNA整合入人类基因组导致E6和E7信使核糖核酸稳定性增加:对子宫颈癌发生的影响
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1654-8. doi: 10.1073/pnas.92.5.1654.
5
Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive cervical carcinoma.在浸润性宫颈癌中,11号染色体11q23上的D11S29位点发生杂合性缺失。
Br J Cancer. 1995 Apr;71(4):814-8. doi: 10.1038/bjc.1995.157.
6
Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells.人乳头瘤病毒16型整合入人类基因组与细胞的选择性生长优势相关。
J Virol. 1995 May;69(5):2989-97. doi: 10.1128/JVI.69.5.2989-2997.1995.
7
Human papillomaviruses and cervical neoplasia. II. Interaction of HPV with other factors.人乳头瘤病毒与宫颈肿瘤。II. 人乳头瘤病毒与其他因素的相互作用。
J Clin Pathol. 1995 Jan;48(1):1-6. doi: 10.1136/jcp.48.1.1.
8
Continued expression of HPV-16 E7 protein is required for maintenance of the transformed phenotype of cells co-transformed by HPV-16 plus EJ-ras.HPV-16 E7蛋白的持续表达是维持由HPV-16与EJ-ras共同转化的细胞的转化表型所必需的。
EMBO J. 1989 Feb;8(2):513-9. doi: 10.1002/j.1460-2075.1989.tb03405.x.
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Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture.由人乳头瘤病毒永生化的上皮细胞在器官型培养中具有癌前特征。
Am J Pathol. 1991 Mar;138(3):673-85.
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J Cancer Res Clin Oncol. 1991;117(5):460-72. doi: 10.1007/BF01612768.