Loss of tumourigenicity of stably ERβ-transfected MCF-7 breast cancer cells

Proliferation of breast cancer cells is mediated by estrogen receptors (ER)-ER alpha and ER beta. At present, contradictory observations complicate the understanding of involvement of ER beta in breast cancer and functional definition of ER beta as a prognostic marker. A stable expression of full length ER beta was established in the ER alpha-positive MCF-7 breast carcinoma cell line to evaluate the role for ER beta in maintenance of cell viability and estrogenic response, as well as proliferation, morphology and cell cycle progression. In order to verify in vivo turnourigenicity of ER beta transfectants were transplanted into nude mice. Transfection of ER beta in MCF-7 resulted in a marginal increase of gelsolin protein expression. Constitutive expression of ER beta resulted in a significant 30% inhibition of cellular growth compared with transfection of the mock vector alone (p=0.043). This reduction in growth was associated a retardation of transition into S-phase of the cell cycle. The in vitro response to 17 beta-estradiol was reversed in cells over-expressing ER beta (p = 0.0 16). However, no difference in response to the antiestrogens tamoxifen and ICI 182,780 was observed in the presence of ER beta. Importantly, over-expression of ER beta prevented establishment and growth of tumours as subcutaneous xenografts in immunodeficient mice in vivo. These observations support the notion that ER beta is a tumour suppressor and is exploitable in terms of cancer prevention, improving therapeutic response or predicting disease progression. (c) 2007 Elsevier Ireland Ltd. All rights reserved.