Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation |
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Authors: | Magaldi Thomas G Almstead Laura L Bellone Stefania Prevatt Edward G Santin Alessandro D DiMaio Daniel |
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Institution: | a Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005, USAb Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063, USAc Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040, USAd Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024, USAe Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028, USA |
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Abstract: | Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells. |
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Keywords: | HPV HeLa cells GM1 Viral tropism Oncogene addiction Cervical cancer SV40 |
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