TY - JOUR
T1 - Epidermal growth factor (EGF) elicits down-regulation of human papillomavirus type 16 (HPV-16) E6/E7 mRNA at the transcriptional level in an EGF-stimulated human keratinocyte cell line
T2 - Functional role of EGF-responsive silencer in the HPV-16 long control region
AU - Yasumoto, S.
AU - Taniguchi, A.
AU - Sohma, K.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1991
Y1 - 1991
N2 - We have found that epidermal growth factor (EGF) elicits negative regulation of human papillomavirus type 16 (HPV-16) E6/E7 at the mRNA level in the HPV-16-immortalized human keratinocyte cell line (PHK160b). This down-regulation of HPV-16 E6/E7 expression was achieved when the cells were stimulated to proliferate with the concomitantly enhanced c-myc expression by EGF in a dose-dependent manner. By using partly synchronized PHK160b cells, negative and positive regulations of the HPV-16 E6/E7 expression was correlated to EGF-linked cell cycle events in this particular human keratinocyte cell line. In order to study transcriptional control mechanisms of the HPV-16 E6/E7, transient expression assays were performed with CAT expression plasmids that the transcription could be directed by the 5'-deleted HPV-16 long control region (LCR) including the virus P97 promoter. We demonstrated that the HPV-16 LCR contained EGF-responsive elements and that a predominant silencer activity was mapped in the proximal 124-bp region (EGFRE) of the LCR. This restricted LCR region had significant influence on HPV-16-homologous promoters in lowering the CAT expression in the presence and absence of EGF. EGFRE was thus considered to be a conditional transcription-controlling element on HPV-16 E6/E7 expression in this EGF-responsive human keratinocyte cell line. This suggests that specific sequences in the LCR play a critical part in the EGF-induced down-regulation of E6/E7 expression at the transcriptional level. Since the results obtained from the transient expression assay agreed with the mode of expression of the endogenous HPV-16 E6/E7, the present study strongly suggests that the transcriptional regulation of the HPV-16 E6/E7 oncogene is mediated by growth-related specific cellular factors interacting with HPV-16 LCR elements.
AB - We have found that epidermal growth factor (EGF) elicits negative regulation of human papillomavirus type 16 (HPV-16) E6/E7 at the mRNA level in the HPV-16-immortalized human keratinocyte cell line (PHK160b). This down-regulation of HPV-16 E6/E7 expression was achieved when the cells were stimulated to proliferate with the concomitantly enhanced c-myc expression by EGF in a dose-dependent manner. By using partly synchronized PHK160b cells, negative and positive regulations of the HPV-16 E6/E7 expression was correlated to EGF-linked cell cycle events in this particular human keratinocyte cell line. In order to study transcriptional control mechanisms of the HPV-16 E6/E7, transient expression assays were performed with CAT expression plasmids that the transcription could be directed by the 5'-deleted HPV-16 long control region (LCR) including the virus P97 promoter. We demonstrated that the HPV-16 LCR contained EGF-responsive elements and that a predominant silencer activity was mapped in the proximal 124-bp region (EGFRE) of the LCR. This restricted LCR region had significant influence on HPV-16-homologous promoters in lowering the CAT expression in the presence and absence of EGF. EGFRE was thus considered to be a conditional transcription-controlling element on HPV-16 E6/E7 expression in this EGF-responsive human keratinocyte cell line. This suggests that specific sequences in the LCR play a critical part in the EGF-induced down-regulation of E6/E7 expression at the transcriptional level. Since the results obtained from the transient expression assay agreed with the mode of expression of the endogenous HPV-16 E6/E7, the present study strongly suggests that the transcriptional regulation of the HPV-16 E6/E7 oncogene is mediated by growth-related specific cellular factors interacting with HPV-16 LCR elements.
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U2 - 10.1128/jvi.65.4.2000-2009.1991
DO - 10.1128/jvi.65.4.2000-2009.1991
M3 - Article
C2 - 1848315
AN - SCOPUS:0026069629
VL - 65
SP - 2000
EP - 2009
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 4
ER -