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

dc.contributor.authorBhat-Nakshatri, P.
dc.contributor.authorCampbell, R. A.
dc.contributor.authorPatel, N. M.
dc.contributor.authorNewton, T. R.
dc.contributor.authorKing, A. J.
dc.contributor.authorMarshall, M. S.
dc.contributor.authorAli, S.
dc.contributor.authorNakshatri, H.
dc.contributor.departmentSurgery, School of Medicineen_US
dc.date.accessioned2023-01-10T21:46:00Z
dc.date.available2023-01-10T21:46:00Z
dc.date.issued2004-02
dc.description.abstractOestrogen 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationBhat-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), Article 4. https://doi.org/10.1038/sj.bjc.6601541en_US
dc.identifier.issn1532-1827en_US
dc.identifier.urihttps://hdl.handle.net/1805/30897
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.isversionof10.1038/sj.bjc.6601541en_US
dc.relation.journalBritish Journal of Canceren_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0*
dc.sourcePublisheren_US
dc.subjectBiomedicineen_US
dc.subjectCancer Researchen_US
dc.subjectDrug Resistanceen_US
dc.titleTumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression functionen_US
dc.typeArticleen_US
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