Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function

P. Bhat-Nakshatri, R. A. Campbell, N. M. Patel, T. R. Newton, A. J. King, M. S. Marshall, S. Ali, H. Nakshatri

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Oestrogen receptor alpha (ERα) is an oestrogen-activated transcription factor, which regulates proliferation and differentiation of mammary epithelial cells by activating or repressing gene expression. ERα is a critical prognostic indicator and a therapeutic target for breast cancer. Patients with tumours that express higher level of ERα have better prognosis than patients with tumours that are ERα negative or express lower level of ERα. Better prognosis in ERα-positive patients is believed to be due to repression of proinvasive gene expression by ERα. Oestrogen receptor alpha represses gene expression by transrepressing the activity of the transcription factors such as nuclear factor-kappaB or by inducing the expression of transcriptional suppressors such as MTA3. In this report, we show that ERα transrepresses the expression of the proinvasive gene interleukin 6 (IL-6) in ERα-negative MDA-MB-231 breast cancer cells stably overexpressing ERα. Using these cells as well as ERα-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis factor alpha (TNFα) and the phosphatidylinositol-3-kinase (PI3-kinase) modulate transrepression function of ERα by reducing its stability. From these results, we propose that TNFα expression or PI3-kinase activation lead to reduced levels of ERα protein in cancer cells and corresponding loss of transrepression function and acquisition of an invasive phenotype.

Original languageEnglish (US)
Pages (from-to)853-859
Number of pages7
JournalBritish Journal of Cancer
Volume90
Issue number4
DOIs
StatePublished - Feb 23 2004

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Keywords

  • IL-6
  • Oestrogen receptor
  • Pl3-kinase
  • Transrepression
  • Tumour necrosis factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bhat-Nakshatri, P., Campbell, R. A., Patel, N. M., Newton, T. R., King, A. J., Marshall, M. S., Ali, S., & Nakshatri, H. (2004). Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function. British Journal of Cancer, 90(4), 853-859. https://doi.org/10.1038/sj.bjc.6601541