Matlashewski G, Osborn K, Banks L, Stanley M, Crawford L
Institute of Parasitology, McGill University, Macdonald College, Ste.-Anne-de-Bellevue, Quebec, Canada.
Int J Cancer. 1988 Aug 15;42(2):232-8. doi: 10.1002/ijc.2910420215.
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.
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。