Regulation of spontaneous and TNF/IFN-induced IL-6 expression in two human ovarian-carcinoma cell lines

Int J Cancer. 1999 Jul 19;82(2):244-9. doi: 10.1002/(sici)1097-0215(19990719)82:2<244::aid-ijc15>;2-n.


Autocrine and paracrine production of interleukin-6 (IL-6) is considered to be involved in the ongoing proliferation of ovarian-cancer cells. In view of the variability in IL-6 expression between various ovarian-cancer cells, we questioned whether differences in IL-6-gene regulation might be observed in ovarian tumor cells with and without IL-6 expression. The CAOV-3 cell line spontaneously secreted IL-6, which was enhanced by tumor necrosis factor-alpha (877 +/- 89 vs. 8,452 +/- 1,762 pg/ml, x +/- sd, p < 0.01). The electrophoretic mobility shift assay (EMSA) demonstrated that basic IL-6 expression was associated with DNA binding of activator protein-1 (AP-1) and nuclear factor IL-6 (NF-IL6). Nuclear factor kappa-B (NF-KB), which consisted mainly of p65-NF-KB was induced in response to TNF-alpha stimulation. A2780 cells did not express IL-6, either spontaneously or after stimulation with TNF-alpha. EMSAs, showed spontaneous AP-1 but no NF-IL6 or NF-KB DNA binding. TNF-alpha stimulation enhanced AP-1 and induced NF-KB but no NF-IL6 DNA binding in these cells. NF-IL6 protein, however, was detected in nuclear extracts of these cells by Western blotting. In contrast, IL-6-promoter transfection studies showed no difference in promoter activation between CAOV-3 and A2780. This study reveals that differential IL-6-gene expression observed in ovarian-cancer cell lines is independent of NF-IL6 activation.

MeSH terms

  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Promoter Regions, Genetic
  • Protein Binding / drug effects
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Analysis, DNA
  • Stimulation, Chemical
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • DNA, Neoplasm
  • Interleukin-6
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma