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1 Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
2 Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Mannitoba, Canada
3 Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada
(Requests for offprints should be addressed to L C Murphy, Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Ave., Winnipeg, Manitoba R3E 0 V9, Canada; Email: lcmurph{at}cc.umanitoba.ca)
To investigate the effect of altered oestrogen receptor (ER)
and ERß expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERß1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERß1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERß1 did not affect endogenous levels of ER
but increased progesterone receptor (PR) levels. Over-expression of ERß1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ER
. In oestrogen-replete conditions, over-expression of ERß1 but not ER
reduced proliferation. Over-expression of ERß1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERß1 in the presence of an endogenously expressed ER
was associated with tamoxifen sensitivity but may negatively modulate ER
-mediated growth. However, not all ER
activities were inhibited since endogenous PR expression was increased by both ER
and ERß1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERß expression as well as ERß expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERß1 expression in ER-positive breast cancer.
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