Changes in oestrogen receptor-alpha and -beta during progression to acquired resistance to tamoxifen and fulvestrant (Faslodex, ICI 182,780) in MCF7 human breast cancer cells

The Journal of Steroid Biochemistry and Molecular Biology
L E ShawP D Darbre

Abstract

Cell culture models of antioestrogen resistance often involve applying selective pressures of oestrogen deprivation simultaneously with addition of tamoxifen or fulvestrant (Faslodex, ICI 182,780) which makes it difficult to distinguish events in development of antioestrogen resistance from those in loss of response to oestrogen or other components. We describe here time courses of loss of antioestrogen response using either oestrogen-maintained or oestrogen-deprived MCF7 cells in which the only alteration to the culture medium was addition of 10(-6) M tamoxifen or 10(-7) M fulvestrant. In both oestrogen-maintained and oestrogen-deprived models, loss of growth response to tamoxifen was not associated with loss of response to fulvestrant. However, loss of growth response to fulvestrant was associated in both models with concomitant loss of growth response to tamoxifen. Measurement of oestrogen receptor alpha (ERalpha) and oestrogen receptor beta (ERbeta) mRNA by real-time RT-PCR together with ERalpha and ERbeta protein by Western immunoblotting revealed substantial changes to ERalpha levels but very little alteration to ERbeta levels following development of antioestrogen resistance. In oestrogen-maintained cells, tamoxifen resi...Continue Reading

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Citations

Nov 21, 2007·Breast Cancer Research and Treatment·Matthew Ellis, Cynthia Ma
Aug 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Gary H PerdewTimothy V Beischlag
Jul 25, 2012·Molecular and Cellular Biology·Khalid HilmiSylvie Mader
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Nov 11, 2020·Journal of Applied Toxicology : JAT·Abdullah Farasani, Philippa D Darbre

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