Implementing Fully Humanised Methods to Examine How the Endocrine Disrupting Chemical Bisphenol A Contributes to Breast Cancer Development
Institution: University of Aberdeen
Corresponding Researcher: Valerie Speirs
Publication Link(s): NA
Data Link(s): Data can be provided upon request.
Keyword(s): NA
Summary
Breast cancer is the most common cancer worldwide, equating to 1 in every 4 cancer diagnoses. Many breast cancer risk factors exist including age, high mammographic density (MD) and exposure to endocrine disrupting chemicals such as the estrogen mimetic bisphenol A (BPA). BPA, used to produce many plastic items can leach from these products, leading to unintentional daily exposures. Research suggests long-term, low-level BPA exposure may influence breast carcinogenesis, yet exact molecular mechanisms remain incompletely understood. This thesis aimed to identify novel BPA contributions to breast carcinogenesis, whilst also determining biological characteristics of MD and whether these two breast cancer risk factors together potentially influence malignant transformation. Bioinformatic analysis uncovered a strong lipophilic signature between non-malignant and cancerous breast tissues, with BPA regulating several genes differentially expressed between these two phenotypes. Low-level BPA exposure increased lipophilic CD36 and PPARγ gene expression within epithelial cells and stromal fibroblasts generated from tissue of high and low MD, with cell growth also elevated after chronic exposures. Cancer-associated adipocyte (CAA) size was significantly smaller than distally located adipocytes, irrespective of MD status. However, an inverse relationship between CAA size and MD was identified in healthy individuals but a positive association was seen in overweight counterparts, likely due to adipocyte hypertrophy and subsequent inflammation seen with elevated BMI. To analyse how BPA might affect breast tissue, a fully humanised 3D in vitro model of normal breast was produced with the aim of using this as a more physiologically relevant model to test the effects of BPA. However, there was insufficient time to address this fully.
