Breast cancer is a major concern worldwide as it accounts for one of the highest causes of death. Oestrogen which is widely known for its growth-promoting function in mammary gland has been linked to breast cancer pathogenesis. Oestrogen exerts its effect upon binding to oestrogen receptors mainly ERα. The presence of ERα in breast cancer has become a prognostic and predictive marker in response to endocrine therapy. Transcription factors are proteins that regulate gene expressions by interacting with specific DNA sequences. AP-2γ, which is implicated in the initiation and progression of breast cancer via ErbB2 and ERα, is a member of AP-2 transcription factors. Forkhead box M1 (FOXM1) belongs to the family of Forkhead box transcription factor. High levels of FOXM1 expression are associated with the development and progression of breast cancer. In this study, the relationship between AP-2γ and FOXM1 were explored. The results suggest a direct association of AP-2γ and FOXM1 in MCF-7 cells and in MCF-7 derived anti-oestrogen resistant cell line, MLET2. Taken together, this work does not only identify the role of AP-2γ in endocrine sensitive cell line, it also reveals that AP-2γ might play a role in endocrine resistance. However, it also shows that AP-2γ may not be the key regulator of FOXM1 in breast cancer where other factors may have a greater influence on FOXM1. Endocrine resistance in breast cancer is a hurdle in hormonal therapy. Oestrogen receptor (ERα) which plays a pivotal role in breast cancer progression, contributes to the development of endocrine resistance. Forkhead transcription factors are also known to be involved in the development and progression of breast cancer. This work also identifies the role of FOXA1, FOXM1, FOXC2 and ERα in endocrine sensitive and resistant cell lines. Taken together, the results show that FOXA1 may not be a key regulator of FOXM1 in MCF-7 cells. However, over-expression of FOXA1 in MDA-MB-231 cell line led to slight reduction in FOXM1 and FOXC2 at translational levels suggesting that FOXA1
may play an important role in regulating those transcription factors. When the cell lines were treated with anti-oestrogen, tamoxifen and ICI, high levels of FOXM1 and FOXC2 were detected in most endocrine resistant cells compared to MCF-7 cells suggesting potential mediators for endocrine resistance. However, high levels of FOXA1 were observed in ERα-expressing cell lines which are associated with better prognosis. In addition to ERα, AP-2γ and Forkhead transcription factors may be potential therapeutic targets for breast cancer. However, more studies should be conducted to validate the current findings.