Influence of Antiestrogen on TGF - BETA Mediated Signaling in Breast Cancer

Abstract

Breast cancer is the second most common malignancy in Indian women. Breast carcinogenesis is a multistep process controlled by many hormones, growth factors and cytokines. Currently, there are three important markers Estrogen receptor (ER), Progesterone receptor (PR), Epidermal Growth Factor Receptor-2 (Her-2) are being used for the selection of treatments in clinical practice however, complete cure or no recurrence is not possible. In the adjuvant set up, ER, PR positive patients were given hormonal treatment chiefly antiestrogens (e.g. Tamoxifen). Amongst them 33% of patients were showing non responsiveness/resistance and due to that the tumor will recur. The another problem is there is no adjuvant treatment for Triple negative patients (ER-ve, PR-ve,HER-2-ve). The reason or cause for the development of resistance/non-responsiveness is not explored till date. It has been shown that, the growth inhibitory effect of antiestrogens is mediated by activation of Transforming Growth Factor Beta (TGF-Beta) and that will induce the development of antiestrogens resistance. The level of TGF-Beta is enhanced by Tamoxifen treatment which leads to suppression of immune response affecting both CD4 and CD8 T cells. Moreover, the role of this TGF-Beta is very important cytokine and its dual role has been one of the cause of breast tumorigenesis. In addition to that TGF-Beta is also important in Epithelial Mesenchymal Transition (EMT), Angiogenesis, cell proliferation and immunotherapy. Hence, it is important to find out the role and expression of TGF-Beta in the antiestrogen resistance and identifying the function as Immunosuppresor . In the current study, the influence of TGF-Beta signaling in antiestrogen treatment will be investigated.