Estrogen Receptors and Xenoestrogen Exposure Cocktails – A New Approach to Breast Cancer Risk
Samantha Dudley - Supervised by Professor Ian Shaw (SPCS) and Professor Ann Richardson (School of Health Sciences)
PhD Candidate, School of Physical and Chemical Sciences
Time & Place
Tue, 27 Nov 2018 13:00:00 NZDT in Room 701, Level 7, WEST Building
All are welcome
Breast cancer is an important estrogen receptor (ER) mediated disease driven by estrogen occupancy of the ER. Interactions with ERs rely on specific features of the estrogen ligand (hydroxyl groups separated by hydrophobicity). If these features occur on other molecules they are likely to mimic estrogens (i.e. xenoestrogens). Until recently, ERs were thought to have only a single binding cleft (the ligand binding cleft (LBC)) which determines activity; a second binding cleft (known as activation function (AF)-2) was discovered later. AF-2 is intimately related to LBC both in its location and function.1 Therefore, ER activity is controlled by the interplay between these two binding sites.
Understanding how xenoestrogens interact with these sites and the biological implications of these interactions are paramount in the context of breast cancer risk. In addition, understanding individual xenoestrogen exposure scenarios and the age dependent effects of these xenoestrogen exposures have on people are crucial in recognising the role of xenoestrogen exposures in a breast cancer risk context. Increasing our understanding of the biological implications of xenoestrogen exposures could lead to the development of new breast cancer preventative strategies.
The talk will explore the complex xenoestrogen exposures (e.g. dietary phytoestrogens)2 in Canterbury women and their daughters, including a small cohort study which identified a number of xenoestrogens in women’s blood. It will discuss the positive (additive) and negative (ameliorative) effects on of xenoestrogen exposure studies in breast cancer cell model systems and the significance of these implications for the biological effects of complex cocktails humans are exposed to on a daily basis. In addition, in silico studies will be discussed highlighting the intimate connection between LBC and AF-2 and new evidence showing some xenoestrogens interacting at both binding sites. Bringing together these three diverse stands of investigation will add to our understanding of ERs, xenoestrogen risk factors and the importance in the aetiology of breast cancer.
1. Ye, H.; Dudley, S. Z.; Shaw, I. C., Intimate estrogen receptor-α/ligand relationships signal biological activity. Toxicology 2018, 408, 80-87.
2. Ye, H.; Dudley, S. Z.; Shaw, I. C., Escherichia coli biotransformation of daidzein fermentation products from soy-based foods—relevance to food oestrogenicity- based functionality. Int. J. Food Sci. Technol. 2017, 52, 1082-1091.