Abstract:
Chemo-resistance is the major cause of clinical failure in breast cancer and more complete understanding of factors contributing to drug resistance would improve treatment outcome. Trefoil factor 1 (TFF1) is a secreted protein which is expressed mainly in the gastro-intestinal tract. TFF1 is one of the major factors involved in restitution and maintenance of the gut barrier. During restitution, TFF1 modulates cell proliferation, cell migration, and angiogenesis while inhibiting apoptosis, processes necessary for rapid gut repairing. Elevated levels of TFF1 expression is observed in breast cancer, indicating that selective up-regulation of TFF1 may have a role in oncogenesis. The putative roles of TFF1 in cancer progression include cancer cell proliferation, migration, apoptosis, and angiogenesis. Recently, it was demonstrated that TFF1 modulates the immune response and cell differentiation. Although the oncogenic function of TFF1 in breast cancer has been documented by various studies, the relationship between TFF1 and chemo-resistance has not been investigated. The overall purpose of this project was to investigate the potential role of TFF1 in chemo-resistance in mammary carcinoma. TFF1 transfected MCF7 and T47D cells were utilised to analyse the effect of TFF1 over-expression on the cellular response to doxorubicin and paclitaxel. Forced expression of TFF1 induced resistance to doxorubicin and paclitaxel and depletion of endogenous TFF1 by siRNA re-sensitised the response. Therefore, antagonisation of TFF1 function could be used in breast cancer treatment to enhance the response to certain chemotherapeutic drugs, and to improve clinical outcome.
