Induction of cell-cycle arrest in cervical cancer cells by the human immunodeficiency virus type 1 viral protein R

Eugene P. Toy, Lorna Rodríguez-Rodríguez, Dennis McCance, John Ludlow, Vicente Planelles

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Objective: To determine the ability of the human immunodeficiency virus type 1 (HIV-1) gene vpr to induce cell-cycle arrest in cervical cancer cells with or without human papillomavirus (HPV) type 16 E6 or E7 expression.Methods: High- and low-level expression vectors for vpr (designated pVPR(HIGH) and pVPR(LOW), respectively) were used in conjunction with HPV-16 E6 or E7 vectors to transfect HPV-negative C33A cervical cancer cells. Vpr expression vectors encode a cell surface marker gene, murine Thy-1, for specific detection of transfected cells. Dual staining for the surface molecule Thy-1 and DNA content was used to determine cell-cycle profile and G2-phase arrest.Results: C33A cells not expressing HPV-16 E6 showed some but not maximal G2-phase arrest when transfected with pVPR(HIGH) alone (43.2% of cells in the G2 phase). Addition of HPV-16 E6 or E6 plus E7 to pVPR(HIGH) substantially increased the percentages of cells in the G2 phase (51.3% and 53.0%, respectively). Cotransfection with pVPR(HIGH) and HPV-16 E7 did not increase significantly the percentage of cells in the G2 phase compared with pVPR(HIGH) alone (40.6% versus 43.2%). In transfections involving pVPR(LOW), a slight degree of G2-phase arrest was observed when Vpr was expressed alone (29.0% of cells in the G2 phase) or in cotransfection with HPV-16 E7 (33.2% of cells), and G2-phase arrest was augmented with the addition of HPV-16 E6 (41.7%) or E6 plus E7 (45.7%).Conclusion: Cervical cancer cells are susceptible to cell-cycle arrest induced by HIV-1 vpr. This effect is exacerbated by coexpression of HPV-16 E6, although E6 alone is incapable of inducing any detectable G2-phase arrest, suggesting that E6 and VPR share links in cell-cycle signaling pathways. Copyright (C) 2000 The American College of Obstetricians and Gynecologists.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalObstetrics and gynecology
Volume95
Issue number1
DOIs
StatePublished - Jan 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology

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