Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes.
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.
Chen
L
L
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Ashe
S
S
Singhal
M C
MC
Galloway
D A
DA
Hellström
I
I
Hellström
K E
KE
D000818:Animals; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D005814:Genes, Viral / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16