Influence of Antiestrogen on TGF – B Signalling in Hormone Responsive Breast Cancer

Abstract

Breast cancer is a heterogeneous disease and involves multiple steps. It is controlled by many hormones, growth factors and cytokines. Currently, there are three important markers in which Estrogen receptor (ER), Progesterone receptor (PR) are hormone receptors and its presence is being used as diagnostic and predictive tool for therapeutic selection. Approximately 72.2% of breast cancers are hormone receptor positive. Estrogen receptor (ER) and Progesterone receptor (PR) positive patients were given hormonal treatment antiestrogen (Tamoxifen). The current problem in hormonal therapy is its resistance or non-responsiveness. The possible reason for mechanism of resistance and/or non-responsiveness is unknown. Third predictive marker is Epidermal Growth Factor Receptor-2 (HER-2) and Herceptin, a monoclonal antibody treatment is being given as therapy for HER-2 positive patients. Moreover, there are many markers being investigated in which Transforming Growth Factor β (TGF-β) is one of the surrogate markers. It is a pluripotent cytokine and known for its dual role in breast tumorigenesis. It has been reported that TGF-Beta is increased during antiestrogen treatment and growth inhibitory effect of Antiestrogen is mediated by activation of TGF-Beta. However, the mechanism is yet to be explored. It has been hypothesized that the possible reason of activation of TGF-Beta signaling will be either through alternative signaling of ER which is responsible to activate TGF-β during Antiestrogen treatment. In our study we estimate the TGF-β1, TGF-β2, SMAD-3 and SMAD-4 in hormone receptor positive (T47D) breast cancer cells during antiestrogen treatment using ELISA.