Disruption of the human papillomavirus type 16 E2 gene protects cervical carcinoma cells from E2F-induced apoptosis.
Human papillomavirus type 16 (HPV-16) is a DNA tumour virus that has been implicated in the development of cervical cancer. In non-transformed HPV-infected cells, the HPV E2 protein regulates transcription of the viral E6 and E7 oncogenes. Malignant transformation is usually accompanied by disruption of the E2 gene and consequent deregulated expression of E6 and E7. Here we show that re-introduction of the HPV-16 E2 protein into an HPV-16-transformed cervical carcinoma cell line results in a decrease in growth rate and, in the absence of serum growth factors, cell death via apoptosis. E2 expression increases E6/E7 mRNA levels. This brings about an increase in E7 protein levels, which in turn leads to an increase in free E2F, a condition that has previously been shown to induce apoptotic cell death. Despite the increase in E6 mRNA there is no detectable E6 protein in these cells and E2 expression does not reduce the activity of a p53-responsive promoter. Our data suggest that disruption of the E2 gene produces HPV-transformed cells that are less liable to undergo apoptosis and, therefore, more likely to form cervical tumours.
Sanchez-Perez
A M
AM
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Soriano
S
S
Clarke
A R
AR
Gaston
K
K
D017209:Apoptosis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000821:virology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D050684:E2F Transcription Factors; D009856:Oncogene Proteins, Viral; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors