Obesity is the most significant public health problem in the developed world and it is well recognised that obesity increases risk of cancer development and recurrence. The most striking relationship between obesity and cancer is seen in endometrial cancer which is considered to be the classic obesity-related cancer. Estrogen is recognised to play a key role in endometrial cancer through its effect on cell proliferation and survival and the majority of endometrial cancers express the estrogen receptor, ERα. Based on classical teaching that still predominates today that obesity results in increased levels of circulating estradiol as well as increased stores of estrogen in adipose tissue, many have presumed that the majority of obese patients will activate estrogen signalling pathways which may promote the development of the cancer.
This project will investigate the molecular basis of estrogen signalling in the endometrium and its functional relationship with obesity. We have developed a model system of co-culturing endometrial cancer cells with fat. Estrogen-responsive genes will be identified and an assessment of how their expression and methylation status is altered by fat will be performed. Although this application focuses on the link between obesity, endometrial cancer and estrogen signalling, this model system will be applicable to other cancer types and signalling systems to study the mechanisms of obesity-related carcinogenesis.