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

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.