Inhibition of radiation-induced apoptosis lay dexamethasone in cervical carcinoma cell lines depends upon increased HPV E6/E7

M. C. Kamradt, N. Mohideen, E. Krueger, S. Walter, Andrew T M Vaughan

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Through a glucocorticoid-responsive promoter, glucocorticoids can regulate the transcription of the human papillomavirus (HPV) E6 and E7 viral genes which target the tumour suppressor proteins p53 and Rb respectively. In C4-1 cells. the glucocorticoid dexamethasone up-regulated HPV E6/E7 mRNA and decreased radiation-induced apoptosis. In contrast, dexamethasone had no effect on apoptosis of cells that either lack the HPV genome (C33-a) or in which HPV E6/E7 transcription is repressed by dexamethasone (SW756). Irradiated C4-1 cells showed increased p53 expression, while dexamethasone treatment prior to irradiation decreased p53 protein expression. In addition, p21 mRNA was regulated by irradiation and dexamethasone in accordance with the observed changes in p53. Overall, glucocorticoids decreased radiation-induced apoptosis in cervical carcinoma cells which exhibit increased HPV E6/E7 transcription and decreased p53 expression. Therefore, in HPV-infected cervical epithelial cells, p53-dependent apoptosis appears to depend upon the levels of HPV E6/E7 mRNA. (C) 2000 Cancer Research Campaign.

Original languageEnglish (US)
Pages (from-to)1709-1716
Number of pages8
JournalBritish Journal of Cancer
Volume82
Issue number10
StatePublished - 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Cervical carcinoma
  • Dexamethasone
  • HPV
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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