Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes

Lieping Chen, Stephanie Ashe, Mitra C. Singhal, Denise A. Galloway, Ingegerd Hellström, Karl Erik Hellström

Research output: Contribution to journalArticlepeer-review

Abstract

The human papillomavirus type 16 (HPV-16) is a DNA tumor virus highly associated with cervical carcinoma. Viral DNA from HPV-16 is found in primary tumors and their metastatic lesions. To investigate the role of HPV-16 oncoproteins in the development of cancer metastasis, the E6 and E7 genes from HPV-16 were inserted into retrovirus and introduced into nonmetastatic mouse cell lines. Expression of either of the viral genes from HPV-16 made the cells metastatic in nude mice. In contrast, expression of the E6 and E7 genes of HPV type 6 (HPV-6b), which is frequently found in nonmalignant HPV-associated diseases, did not. The metastatic ability of cells transduced with viral genes of HPV-16 did not correlate with their growth rate or sensitivity to destruction by natural killer cells. Our results demonstrate that expression of oncogenic proteins of HPV-16 can cause tumor metastasis and implicate HPV-16 in an important role regarding the progression of HPV-associated human cancers.

Original languageEnglish (US)
Pages (from-to)6523-6527
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number14
StatePublished - Jul 15 1993
Externally publishedYes

Keywords

  • Cancer metastasis
  • Malignancy
  • Transformation
  • Tumorigenicity

ASJC Scopus subject areas

  • General
  • Genetics

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