Direct activation of oestrogen receptor-α by interleukin-6 in primary cultures of breast cancer epithelial cells

V. Speirs, M. J. Kerin, D. S. Walton, C. J. Newton, S. B. Desai, Stephen Atkin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Interleukin 6 (IL-6) is secreted by breast tumours and shows synergistic activity with 17β-oestradiol (E2), leading to increases in reductive 17β-hydroxysteroid dehydrogenase activity in breast cancer epithelial cells. However, the mechanisms involved are poorly understood. Using short-term epithelia[ cultures established from primary breast tumours, we have examined whether IL-6 could directly affect transcriptional activity of oestrogen reception α (ERα). Tumour epithelial cultures were established from 15 breast tumours, grown to 70% confluence and transiently transfected with a plasmid reporter containing the vitellogenin oestrogen response element and the luciferase coding sequence (ERE-TK-LUC). Following transfection, cells were incubated with E2, IL-6, the pure anti-oestrogen ZM 182780 or combinations of these substances for 48 h. Luciferase activity was then measured in cell lysates. E2 caused a dose-dependent increase in luciferase expression, causing a maximum threefold stimulation at 100 pM. In the presence of IL-6, transcriptional activity was increased by up to 2.5-fold in ERα+ cultures (11/15). In combination with E2, synergistic effects were observed with increases in luciferase activity of up to sixfold over controls. This effect could be blocked by treatment with ZM 182780. Pre-incubation of cells with an antibody directed against the signalling component of IL-6, gp130, was ineffective in blocking the E2 response. This antibody reduced, but did not completely block the effect of IL-6 either alone or in combination with E2, suggesting cross-talk between the two signalling pathways. In conclusion, these results provide evidence for direct transcriptional activation of ERα by IL-6. (C) 2000 Cancer Research Campaign.

Original languageEnglish
Pages (from-to)1312-1316
Number of pages5
JournalBritish Journal of Cancer
Volume82
Issue number7
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Estrogen Receptors
Interleukin-6
Epithelial Cells
Breast Neoplasms
Luciferases
Estrogens
Vitellogenins
Antibodies
Response Elements
Transcriptional Activation
Transfection
Estradiol
Plasmids
Epithelium
Neoplasms

Keywords

  • Breast cancer
  • Interleukin-6
  • Steroids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Direct activation of oestrogen receptor-α by interleukin-6 in primary cultures of breast cancer epithelial cells. / Speirs, V.; Kerin, M. J.; Walton, D. S.; Newton, C. J.; Desai, S. B.; Atkin, Stephen.

In: British Journal of Cancer, Vol. 82, No. 7, 2000, p. 1312-1316.

Research output: Contribution to journalArticle

Speirs, V. ; Kerin, M. J. ; Walton, D. S. ; Newton, C. J. ; Desai, S. B. ; Atkin, Stephen. / Direct activation of oestrogen receptor-α by interleukin-6 in primary cultures of breast cancer epithelial cells. In: British Journal of Cancer. 2000 ; Vol. 82, No. 7. pp. 1312-1316.
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