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KMID : 0385219980080020057
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Korean Journal of Gerontology
1998 Volume.8 No. 2 p.57 ~ p.65
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Induction of Senescence-like State in HeLa Cells by the Expression of Bovine Papillomavirus E2 Gene
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Hwang Eun-Seong
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Abstract
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Previously, acute expression of bovine papillomavirus (BPV) E2 gene has been shown to specifically inhibit the expression of E6/E7 genes in several HPV-positive cervical cancer cell lines including HeLa and HT-3. Down-regulation of E6/E7 transcription by BPV E2 in these cell lines was followed by an accumulation of p53 and hypophosphorylated Rb proteins, and a dramatic reduction in the synthesis of cellular DNA, eventually leading to a stable growth arrest at G1 phase. Here, we examined whether the depletion of E6 and E7 proteins brings in an alteration in the immortalized state of these cancer cell lines. Growth-arrested HeLa cells mostly became enlarged and expressed senescence-associated β-galactosidase (SA-β-Gal) activity, a critical biomarker for cellular senescence. In contrast, SA-β-Gal positive cells were quite rare in E2-transduced population of HT-3 cell line which has a mutant p53 gene, suggesting that BPV E2-mediated E6/E7 depletion induces a senescence-like stae in a wild-type p53-dependent manner. Telomerase activity measured in HeLa cells did not change significantly after induction of growth arrest by BPV E2, indicating that E6 may not be required for maintenance of telomerase activity and that cells can undergo senescence-like state with an intact telomerase activity. These results suggest that in the absence of E6 and E7, HPV-positive cervical cancer cells may undergo a state like senescence, but this event may not be mediated nor accompanied by decrease in telomerase activity. Possibly, restoration of p53 or concomitant induction of p21WAF1/CIP1 may directly induce senescence-like state in HeLa cells.
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KEYWORD
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Senescence, Human papillomavirus, Telomerase, BPV E2, p53
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