Estrogen receptor beta is an important modulator of hormone-related carcinogenesis in the human prostate.

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Prostate cancer is the most common cancer in men, with 214 new cases diagnosed per 1000 men in Europe. Currently, it is the second most common cause of cancer-related death in men.The development of prostate cancer is largely dependent on the male hormone, testosterone and so for many patients initial treatment of the disease involves blocking the production and activity of testosterone in order to suppress the disease. Unfortunately, for many men the cancer subsequently becomes resistant to this treatment and continues to grow in the absence of testosterone. Current chemotherapy treatments are not particularly effective against this hormone resistant prostate cancer (HRPC) and patients survive for an average period of 18 months from the time of HRPC diagnosis.In females, the dominant hormone is estrogen. Estrogen is known to play an important role in the development and growth of breast and ovarian cancers in women. Consequentially, a number of treatments for these diseases are aimed at blocking the production and activity of estrogen in a manner analogous to hormone deprivation treatment of prostate cancer. Estrogen is also present in smaller quantities in men where it regulates a variety of processes in the body. It does this by sending signals to cells using the estrogen receptor. When activated, the estrogen receptor instructs the cell's genetic code (DNA) to create proteins, which in turn influence the behaviour of the cancer cell in a particular way. Recent scientific research has demonstrated that estrogen and one of its receptors, estrogen receptor beta (ERb) play an important role in controlling some of the genetic mechanisms that can give rise to prostate cancer. However, the mechanisms by which ERb regulates cancer-related genes are poorly characterised. In particular, it is thought that when prostate cancer becomes resistant to testosterone deprivation to become HRPC, estrogen may continue to provide a stimulus for cancer growth acting via the estrogen receptor.In my research, I aim to increase understanding of how estrogen and ERb can regulate cancer-related genes in the prostate. I will be studying the effects of estrogen and ERb in order to understand how prostate cancer initially develops and how it becomes resistant to testosterone deprivation. Estrogen receptors are dependent upon a protein in the cell called FoxA1, which acts as bridge to bind the receptor to the DNA enabling it to switch genes on and off. Most of our understanding of FoxA1 and its influence on estrogen receptors comes from the study of breast cancer. At present, it has not been determined if FoxA1 has any function with respect to estrogen receptor in the prostate. By increasing or decreasing levels of FoxA1 in prostate cells and tissue I will explore the role that it plays in the prostate and determine whether it could be a potential drug target to control the progression of prostate cancer.The research will be conducted in the laboratory using cells derived from human prostate cancer tissue as these provide a useful model for studying the disease. I also aim to study prostate tissue obtained from patients undergoing surgery who have given permission for me to do so, in order to see whether some of the findings observed in the cells are also present in 'real-patient' samples.By increasing the understanding of how estrogen influences the development and progression of prostate cancer I aim to find new ways to treat HRPC.