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Identification of estrogen receptor α and Β signalling targets

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dc.contributor.advisor Amoils KD en
dc.contributor.advisor Clausen V en
dc.contributor.author Dahan N en
dc.date.accessioned 2016-09-22T11:19:59Z
dc.date.available 2016-09-22T11:19:59Z
dc.date.created 2001 en
dc.date.submitted 2003 en
dc.identifier.uri http://hdl.handle.net/20.500.11892/111944
dc.description.abstract The oestrogen receptor (ER) functions as a ligand-activated transcription factor regulating the expression of genes containing specific hormone response elements in their promoter regions. Initially, the expression of the two subtypes of the receptor, ERa and ERΒ, was verified in the human breast cancer cell lines, MCF-7, T-47D and MDA-MB-231. RT-PCR revealed that MCF-7 cells expressed ERa, T-47D cells expressed both ERα and ERΒ, and MDA-MB-231 cells did not express either subtype. The effect of endogenously and exogenously expressed ERs on the transcriptional regulatory potential of a variety of promoter elements was investigated in the three cell lines. This was achieved via transient transfection experiments performed with plasmids containing specific promoter elements driving the expression of the reporter gene, secreted alkaline phosphastase (SEAP). ER action at the classical oestrogen response element (ERE) induced a typical pattern of activation in the MCF-7 and MDA-MB-231 cell lines. Treatment with the natural oestrogen, 17Β-oestradiol, enhanced the transcriptional potential of the ERE, whereas the anti-oestrogens, 4-hydroxytamoxifen and ICI 182,780, inhibited it. In the MDA-MB-231 cell line, co-transfection experiments with ER expression plasmids showed that ERα-mediated activation was stronger than ERΒ-mediated activation in the context of the ERE. Analysis of the transcriptional potential of the NFκB promoter element revealed that the ER, when activated by 17Β-oestradiol, inhibited the NFκB pathway in both MCF-7 and MDA-MB-231 cells with no apparent differences between the two subtypes. Interestingly, a possible agonistic activity mediated via the ER was detected with 4-hydroxytamoxifen and ICI 182,780 treatments in MDA-MB-231. Lastly, the activation of the serum response element (SRE) was investigated but no significant up- or down-regulation was observed. No response was detected in the T-47D cells at any of the promoter elements studied, due to the possible unsuitability of this cett line for SEAP reporter studies. en
dc.language English en
dc.title Identification of estrogen receptor α and Β signalling targets en
dc.type Masters degree en
dc.description.degree MSc (Med) en

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