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

Proliferation of breast cancer cells is mediated by estrogen receptors (ER)—ERα and ERβ. At present, contradictory observations complicate the understanding of involvement of ERβ in breast cancer and functional definition of ERβ as a prognostic marker.A stable expression of full length ERβ was established in the ERα-positive MCF-7 breast carcinoma cell line to evaluate the role for ERβ in maintenance of cell viability and estrogenic response, as well as proliferation, morphology and cell cycle progression. In order to verify in vivo tumourigenicity of ERβ transfectants were transplanted into nude mice.Transfection of ERβ in MCF-7 resulted in a marginal increase of gelsolin protein expression. Constitutive expression of ERβ 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 17β-estradiol was reversed in cells over-expressing ERβ (p = 0.016). However, no difference in response to the antiestrogens tamoxifen and ICI 182,780 was observed in the presence of ERβ. Importantly, over-expression of ERβ prevented establishment and growth of tumours as subcutaneous xenografts in immunodeficient mice in vivo.These observations support the notion that ERβ is a tumour suppressor and is exploitable in terms of cancer prevention, improving therapeutic response or predicting disease progression.