Antiestrogens suppress effects of transforming growth factor-β in breast cancer cells via the signaling axis estrogen receptor-α and Y-box Binding Protein-1.

Background: Multifunctional Y-box Binding Protein-1 (YB1) is correlated with a poor outcome in breast cancer. We found YB1 expression to be regulated by antiestrogens commonly used in the hormonal therapy of breast cancer and known as activators of Transforming Growth Factor-beta (TGF beta). Thus, a putative influence of YB1 on TGF beta signaling should be investigated. Materials and Methods: The effect of YB1 on TGF beta signaling was monitored by expression analysis and reporter gene assays in breast cancer cells overexpressing YB1 and treated with antiestrogens. Results: Antiestrogen-mediated inhibition of estrogen receptor-alpha led to a suppression of YB1 protein synthesis. On the other hand, YB1 was found to be an enhancer of TGF beta signaling. Conclusion: High levels of YB1 expression lead to a stimulation of TGF beta pathways, thereby counteracting antihormonal breast cancer therapy and representing a putative resistance mechanism.