PROSTATE CELL STRUCTURE AND FUNCTION IN BPH

良性和恶性疾病在人类前列腺中最常见， 在精囊中很少发生，在 尿道球腺。 在风险上的差异超过一百万倍 这些腺体之间的良性疾病很难理解， 特别是因为腺体位于同一个体内， 相同的遗传基因组和相似的生理学和暴露于 环境风险因素。 我们相信这个谜题的答案 在组织特异性的分子基础上。 我们已经报道了 大鼠前列腺的组织特异性与基因表达相关 组织特异性核基质蛋白，这些蛋白似乎在组织中组织DNA， 一种组织特异性三维结构， 组织特异性基因。 在前列腺癌的动物模型中， 证明了这些核基质蛋白发生的特定变化， 是恶性转化的特征 最近，我们报道说，在 人的前列腺随着BPH的发展， 核基质蛋白的模式和这些变化代表了 与前列腺相关的其他变化的连续变化 癌 虽然BPH和前列腺癌通常发生在不同的区域， 尽管如此，它们可能具有相似的早期分子事件 在他们的转变过程中。 这肯定是一种情况， 累积的遗传事件，其中良性病变的变化也是早期的 结肠癌和膀胱癌的发展中的事件。 我们建议 识别和表征核基质蛋白及其变化 在BPH的发展过程中，并研究它们如何通过后 翻译修饰，特别强调蛋白质 磷酸化和蛋白质甲基化。 我们还报告说， 细胞外基质是能够诱导的组成的变化， 核基质，并与结构变化有关， 细胞的功能。 我们将分离细胞外基质成分， 正常前列腺和良性前列腺增生的人和 并确定它们如何改变前列腺上皮细胞的生长 细胞 核基质组织DNA环结构域和三维结构域。 因此，我们也在设计新的方法， 评估细胞核中的染色质模式以及三维 在BPH的发展过程中，细胞核的组织发生了变化。

Benign and malignant diseases are most common in the human prostate but occur only rarely in the seminal vesicles and not at all in the bulbourethral gland. Well over a one-million fold difference in risk of benign disease between these glands is difficult to understand, particularly since the glands reside within the same individual and have the same inherited genome and similar physiology and exposure to environmental risk factors. We believe the answer to this riddle resides within the molecular basis of tissues specificity. We have reported that the tissue specificity and gene expression of the rat prostate is related to tissue-specific nuclear matrix proteins that appear to organize DNA in a tissue specific three-dimensional structure that dictates the activation of tissue specific genes. In animal models of prostate cancer we have also demonstrated specific changes occurring in these nuclear matrix proteins that characterize malignant transformation. Recently, we reported that in the human prostate with the development of BPH, there is a marked change in the pattern of the nuclear matrix proteins and these changes represent a continuum of changes with additional changes being associated with prostate cancer. While BPH and prostate cancers often develop in different regions of the prostate, they may nevertheless share similar early molecular events in their transformation process. This has certainly been the case in cumulative genetic events where changes in benign lesions are also early events in the development of colon and bladder cancer. We propose to identify and characterize the nuclear matrix proteins and how they change during development of BPH and to study how they may be altered by post- translational modification, with particular emphasis on protein phosphorylation and protein methylation. We have also reported that the extracellular matrix is capable of inducing changes in the composition of the nuclear matrix and that is associated with changes in structure and function of the cell. We will isolate extracellular matrix components from the normal prostate and benign prostatic hyperplasia in both the human and canine and determine how they alter the growth of prostate epithelial cells. The nuclear matrix organizes DNA loop domains and the 3-dimensional higher order chromatin structure, therefore, we are also designing new ways to assess chromatin patterns in the nucleus and how the 3-dimensional organization of the nucleus is altered during development of BPH.