Targeting the Human Papillomavirus E6 and E7 Oncogenes through Expression of the Bovine Papillomavirus Type 1 E2 Protein Stimulates Cellular Motility

التفاصيل البيبلوغرافية
العنوان: Targeting the Human Papillomavirus E6 and E7 Oncogenes through Expression of the Bovine Papillomavirus Type 1 E2 Protein Stimulates Cellular Motility
المؤلفون: Matthew Kofron, Susanne I. Wells, Richard J. Morreale, Monique A. Morrison, Shailaja Akunuru, Yi Zheng
المصدر: Journal of Virology. 85:10487-10498
بيانات النشر: American Society for Microbiology, 2011.
سنة النشر: 2011
مصطلحات موضوعية: biology, Cell growth, Immunology, Viral Oncogene, Motility, Oncogene Proteins, Viral, biology.organism_classification, Microbiology, Transformation and Oncogenesis, Cell biology, DNA-Binding Proteins, HeLa, Viral Proteins, Cell Movement, Cell culture, Cell Line, Tumor, Virology, Insect Science, Cancer cell, Humans, Psychological repression, Bovine papillomavirus 1, Cell Proliferation, Bovine papillomavirus
الوصف: Expression of the high-risk human papillomavirus (HPV) E6 and E7 oncogenes is essential for the initiation and maintenance of cervical cancer. The repression of both was previously shown to result in activation of their respective tumor suppressor targets, p53 and pRb, and subsequent senescence induction in cervical cancer cells. Consequently, viral oncogene suppression is a promising approach for the treatment of HPV-positive tumors. One well-established method of E6/E7 repression involves the reexpression of the viral E2 protein which is usually deleted in HPV-positive cancer cells. Here, we show that, surprisingly, bovine papillomavirus type 1 (BPV1) E2 but not RNA interference-mediated E6/E7 repression in HPV-positive cervical cancer cells stimulates cellular motility and invasion. Migration correlated with the dynamic formation of cellular protrusions and was dependent upon cell-to-cell contact. While E2-expressing migratory cells were senescent, migration was not a general feature of cellular senescence or cell cycle arrest and was specifically observed in HPV-positive cervical cancer cells. Interestingly, E2-expressing cells not only were themselves motile but also conferred increased motility to admixed HeLa cervical cancer cells. Together, our data suggest that repression of the viral oncogenes by E2 stimulates the motility of E6/E7-targeted cells as well as adjacent nontargeted cancer cells, thus raising the possibility that E2 expression may unfavorably increase the local invasiveness of HPV-positive tumors.
تدمد: 1098-5514
0022-538X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a55eb015ef9832a463eee1ede668b270
https://doi.org/10.1128/jvi.05126-11
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....a55eb015ef9832a463eee1ede668b270
قاعدة البيانات: OpenAIRE