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

前列腺癌是男性最常见的癌症，在欧洲，每1000名男性中就有214名新确诊病例。目前，前列腺癌是男性癌症相关死亡的第二大常见原因。前列腺癌的发生在很大程度上依赖于男性激素和睾酮等，因此对许多患者来说，最初的治疗包括阻断睾酮的产生和活性，以抑制疾病。不幸的是，对于许多男性来说，癌症后来对这种治疗产生了抗药性，并在缺乏睾丸素的情况下继续生长。目前的化疗方法对这种激素抵抗型前列腺癌(HRPC)并不是特别有效，患者从HRPC确诊之日起平均存活18个月。在女性中，主要的激素是雌激素。众所周知，雌激素在女性乳腺癌和卵巢癌的发展和生长中发挥着重要作用。因此，针对这些疾病的一些治疗方法旨在阻断雌激素的产生和活性，类似于前列腺癌的激素剥夺治疗。在男性体内，雌激素的含量也较少，它可以调节体内的各种过程。它通过使用雌激素受体向细胞发送信号来做到这一点。当被激活时，雌激素受体指示细胞的遗传密码(DNA)产生蛋白质，这些蛋白质反过来以特定的方式影响癌细胞的行为。最近的科学研究表明，雌激素及其受体之一雌激素受体β(ERb)在控制前列腺癌发生的某些遗传机制中发挥着重要作用。然而，ERb调控癌症相关基因的机制尚不清楚。特别是，人们认为，当前列腺癌对睾丸激素缺乏产生抵抗力，成为HRPC时，雌激素可能会通过雌激素受体继续为癌症的生长提供刺激。在我的研究中，我的目标是增加对雌激素和ERb如何调节前列腺癌相关基因的理解。我将研究雌激素和ERb的作用，以了解前列腺癌最初是如何发展的，以及它是如何对睾丸激素缺乏产生抵抗力的。雌激素受体依赖于细胞中一种名为FoxA1的蛋白质，它起到将受体与DNA结合的桥梁作用，使其能够开关基因。我们对FoxA1及其对雌激素受体的影响的大部分了解来自于对乳腺癌的研究。目前，还没有确定FoxA1是否与前列腺中的雌激素受体有关。通过增加或降低前列腺细胞和组织中FoxA1的水平，我将探索它在前列腺中所起的作用，并确定它是否可能成为控制前列腺癌进展的潜在药物靶点。这项研究将在实验室进行，使用来自人类前列腺癌组织的细胞，因为这些细胞为研究疾病提供了有用的模型。我的目标也是研究从手术患者那里获得的前列腺组织，这些患者得到了我的许可，以了解在细胞中观察到的一些发现是否也存在于真正的患者样本中。通过增加对雌激素如何影响前列腺癌的发展和进展的理解，我的目标是找到治疗高密度前列腺癌的新方法。

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.