Inducible upregulation of oestrogen receptor-β1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells

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Abstract
To investigate the effect of altered oestrogen receptor (ER)α and ERβ expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERβ1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERβ1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERβ1 did not affect endogenous levels of ERα but increased progesterone receptor (PR) levels. Over-expression of ERβ1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ERα. In oestrogen-replete conditions, over-expression of ERβ1 but not ERα reduced proliferation. Over-expression of ERβ1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERβ1 in the presence of an endogenously expressed ERα was associated with tamoxifen sensitivity but may negatively modulate ERα-mediated growth. However, not all ERα activities were inhibited since endogenous PR expression was increased by both ERα and ERβ1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERβ expression as well as ERβ expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERβ1 expression in ER-positive breast cancer.

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