Bomb Pulse Carbon-14 Dating of Prostate Tissues to Elucidate the Origins of BPH

项目摘要 前列腺是老年男性肿瘤最常见的部位，目前仍存在争议 与良性前列腺增生（BPH）中基质和上皮细胞的分子作用有关， 癌在他们的一生中，美国男性有1/6的机会被诊断患有前列腺癌 90%的80岁以上的男性有症状的BPH，导致严重的尿路并发症 [1，2]。然而，人们对导致前列腺疾病的遗传和环境因素知之甚少， 我们对前列腺组织更新和细胞替换率的理解存在很大差距， 以及细胞替换速率的差异如何影响前列腺疾病的发生和进展。 前列腺细胞产生和替换的速度影响一个人的疾病发生的风险， 疾病进展的速度，我们的初步数据表明，前列腺组织中存在巨大的差异， 个人之间的转换。因此，对前列腺组织更新的准确理解具有很高的 潜在挑战现有的前列腺功能和前列腺疾病发生的范例， 实验方法来识别和表征前列腺上皮干细胞库，并重新定义我们的 前列腺组织更新的当前假设。我们的中心假设是前列腺组织有一个 比精囊组织更快的周转，并且在BPH期间，前列腺中有新细胞形成 基质导致前列腺上皮更快的更新。

PROJECT SUMMARY The prostate gland is the most common site of neoplasia in aging men, and there are ongoing controversies pertaining to the molecular roles of stromal and epithelial cells in benign prostate hyperplasia (BPH) and cancer. Throughout their lifetimes, American men have a 1/6 chance of being diagnosed with prostate cancer and 90% of men over the age of 80 have symptomatic BPH leading to significant urinary track complications [1,2]. The genetic and environmental factors contributing to prostate disease, however, are poorly understood, and there are large gaps in our understanding of prostate tissue turnover and the rates of cellular replacement, and how differences in the rate at which cells are replaced impacts prostate disease initiation and progression. The rate at which prostate cells are created and replaced impact a person's risk of disease initiation and the rate of disease progression, and our preliminary data suggests that there are vast differences in prostate tissue turnover between individuals. Thus, an accurate understanding of prostate tissue turnover has the high potential to challenge existing paradigms of prostate function and prostate disease initiation, enable new experimental approaches to identify and characterize prostate epithelial stem cell pools, and re-define our current assumptions of tissue turnover in the prostate. Our central hypothesis is that prostate tissue has a more rapid turnover than seminal vesicle tissue, and that during BPH there is new cell formation in the prostate stroma leading to more rapid turnover of prostate epithelia.