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Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function.
- Source :
- British Journal of Cancer; 2/23/2004, Vol. 90 Issue 4, p853-859, 7p
- Publication Year :
- 2004
-
Abstract
- Oestrogen receptor alpha (ERalpha) is an oestrogen-activated transcription factor, which regulates proliferation and differentiation of mammary epithelial cells by activating or repressing gene expression. ERalpha is a critical prognostic indicator and a therapeutic target for breast cancer. Patients with tumours that express higher level of ERalpha have better prognosis than patients with tumours that are ERalpha negative or express lower level of ERalpha. Better prognosis in ERalpha-positive patients is believed to be due to repression of proinvasive gene expression by ERalpha. 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 ERalpha transrepresses the expression of the proinvasive gene interleukin 6 (IL-6) in ERalpha-negative MDA-MB-231 breast cancer cells stably overexpressing ERalpha. Using these cells as well as ERalpha-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis factor alpha (TNFalpha) and the phosphatidylinositol-3-kinase (PI3-kinase) modulate transrepression function of ERalpha by reducing its stability. From these results, we propose that TNFalpha expression or PI3-kinase activation lead to reduced levels of ERalpha protein in cancer cells and corresponding loss of transrepression function and acquisition of an invasive phenotype. [ABSTRACT FROM AUTHOR]
- Subjects :
- TUMOR necrosis factors
TRANSCRIPTION factors
EPITHELIAL cells
BREAST cancer
GENE expression
INTERLEUKIN-6
ESTROGEN receptors
BREAST tumors
CANCER invasiveness
COMPARATIVE studies
GENES
IMMUNOBLOTTING
INTERLEUKINS
RESEARCH methodology
MEDICAL cooperation
NUCLEOTIDE separation
PHOSPHOTRANSFERASES
PROTEINS
RESEARCH
WESTERN immunoblotting
PHENOTYPES
EVALUATION research
CANCER cell culture
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 90
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 12285341
- Full Text :
- https://doi.org/10.1038/sj.bjc.6601541