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, Harikrishna Nakshatri

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

Phosphatidylinositol 3-Kinase
Estrogen Receptor alpha
Tumor Necrosis Factor-alpha
Gene Expression
Transcription Factors
Breast Neoplasms
Neoplasms
Interleukin-6
Estrogens
Breast
Epithelial Cells
Phenotype
estrophilin
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function. / Bhat-Nakshatri, P.; Campbell, R. A.; Patel, N. M.; Newton, T. R.; King, A. J.; Marshall, M. S.; Ali, S.; Nakshatri, Harikrishna.

In: British Journal of Cancer, Vol. 90, No. 4, 23.02.2004, p. 853-859.

Research output: Contribution to journalArticle

Bhat-Nakshatri, P. ; Campbell, R. A. ; Patel, N. M. ; Newton, T. R. ; King, A. J. ; Marshall, M. S. ; Ali, S. ; Nakshatri, Harikrishna. / Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function. In: British Journal of Cancer. 2004 ; Vol. 90, No. 4. pp. 853-859.
@article{bdc1235996da415fbe0318c9652a968e,
title = "Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function",
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.",
keywords = "IL-6, Oestrogen receptor, Pl3-kinase, Transrepression, Tumour necrosis factor",
author = "P. Bhat-Nakshatri and Campbell, {R. A.} and Patel, {N. M.} and Newton, {T. R.} and King, {A. J.} and Marshall, {M. S.} and S. Ali and Harikrishna Nakshatri",
year = "2004",
month = "2",
day = "23",
doi = "10.1038/sj.bjc.6601541",
language = "English",
volume = "90",
pages = "853--859",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function

AU - Bhat-Nakshatri, P.

AU - Campbell, R. A.

AU - Patel, N. M.

AU - Newton, T. R.

AU - King, A. J.

AU - Marshall, M. S.

AU - Ali, S.

AU - Nakshatri, Harikrishna

PY - 2004/2/23

Y1 - 2004/2/23

N2 - 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.

AB - 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.

KW - IL-6

KW - Oestrogen receptor

KW - Pl3-kinase

KW - Transrepression

KW - Tumour necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=1642296731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642296731&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6601541

DO - 10.1038/sj.bjc.6601541

M3 - Article

VL - 90

SP - 853

EP - 859

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

ER -