Transition to an irreversible state of senescence in HeLa cells arrested by repression of HPV E6 and E7 genes.
Mech Ageing Dev
; 125(1): 31-40, 2004 Jan.
Article
em En
| MEDLINE
| ID: mdl-14706235
ABSTRACT
Inhibition of human papillomavirus (HPV) E6 and E7 transcription by means of the E2 protein of bovine papillomavirus 1 (BPV1) has been shown to induce acute growth arrest in HPV-positive cervical carcinoma cells. This state of arrest is marked by the expression of senescence phenotypes including SA beta-Gal activity and lipofuscin accumulation. In this study, we examined the reversibility of these phenotypes by exogenously expressing the E6 and E7 genes into HeLa cells growth-arrested by the depletion of E6/E7. Re-expression of E7 (but not E6) in 2 days following E2 transduction induced the cells to resume growth. The proliferating cells manifested the phenotype of untreated HeLa cells, suggesting that E7 is the major factor responsible for the continued proliferation and the suppression of the senescence phenotype in cervical carcinoma cells. However, E7 in 5 days following E2 transduction did not prevent HeLa cells from entering the senescent state, indicating that the arrested state becomes irreversible. Our results suggest that, upon depletion of the viral oncoproteins, a senescent state is irreversibly induced in HeLa cells after a period of commitment. The status and cellular location of certain factors involved in signal transduction and cell cycle control was altered as well along with this irreversibility transition.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células HeLa
/
Proteínas Oncogênicas Virais
/
Senescência Celular
/
Proteínas de Ciclo Celular
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article