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: Functional role of EGF-responsive silencer in the HPV-16 long control region

S. Yasumoto, A. Taniguchi, K. Sohma

研究成果: Article査読

37 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2000-2009
ページ数10
ジャーナルJournal of Virology
65
4
DOI
出版ステータスPublished - 1991
外部発表はい

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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「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: Functional role of EGF-responsive silencer in the HPV-16 long control region」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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