NORMAL AND NEOPLASTIC PROSTATE

蛋白质磷酸化是一种重要的调控机制。 细胞功能，包括基因组调节和细胞增殖。 因此，对蛋白激酶系统的研究在适当的情况下 实验模型目前引起了人们的浓厚兴趣。对于许多人来说 多年来，该实验室一直专注于蛋白激酶CK2，因为它与 来控制前列腺的生长。CK2是一个多潜能的信使- 独立的丝裂原/酪氨酸激酶。大量证据已经出现，证明了它的 在控制正常细胞生长和增殖方面的作用。谦虚 其活动的失调也与异常生长和 研究表明它参与了肿瘤的发生过程。我们的工作是 前列腺癌组织中CK2的表达与上述结论一致。因此，我们的校长 这项正在进行的研究的假设是蛋白激酶CK2发挥作用 在控制前列腺生长及其失调方面起着重要作用的是 与前列腺瘤有关。本文件中提出的具体目标 CK2生物学知识的更新应用 正常和肿瘤性生长，代表着一种合乎逻辑的发展和 正在进行的研究的扩展。 第一个目标是继续调查所涉及的机制 在生化/生物学方面，CK2的功能与 前列腺癌中CK2的NM状态分析 与格里森等级有关。第二个目标是利用CK2 转基因模型中的信号研究其参与的机制 致癌过程。第三个目标是将CK2信号作为 干扰前列腺生长的潜在部位。 第一个目标的意义在于它对 关于信号调节的基础知识，这对 细胞存活和生长控制。第二个目标的意义 它将导致新的转基因的发展，这将 为研究CK2在脑内的功能作用提供了一个模型 前列腺癌的发生过程，此外，还可能产生一种 研究前列腺癌进展的新模型。这个 第三个目标的意义与其贡献的潜力有关 前列腺癌基因治疗方法的新见解。 总之，这些研究将从根本上提供重要的新的 关于CK2功能活性及其机制的信息 前列腺癌生物学的意义和潜在的治疗方法 目标。

Protein phosphorylation is a significant mechanism in the control of cellular functions, including genomic regulation and cell proliferation. Thus, investigations of protein kinase systems in appropriate experimental models are of intense current interest. For a number of years, this laboratory has focused on protein kinase CK2 as it relates to prostatic growth control. CK2 is a multipotential messenger- independent ser/thr kinase. Considerable evidence has emerged for its role in the control of normal cell growth and proliferation. Modest dysregulation in its activity is also related to abnormal growth and studies suggest its involvement in the oncogenic process. Our work on CK2 in the prostate accords with these conclusions. Thus, our principal hypothesis for this ongoing research is that protein kinase CK2 plays a fundamental role in prostatic growth control and its dysregulation is associated with prostatic neoplasia. The specific aims set forth in this renewal application arise from the knowledge gained on CK2 biology in normal and neoplastic growth and represent a logical progression and expansion of the ongoing studies. The first goal is to continue investigations of the mechanisms involved in biochemical/biological aspects of CK2 function in relation to prostatic growth, and to analyze the NM status of CK2 in prostate cancer in relation to the Gleason grade. The second goal is to utilize the CK2 signal in a transgene model to study mechanism of its involvement in the oncogenic process. The third goal is to target the CK2 signal as a potential locus for interference of growth in the prostate. The significance of the first aim relates to its contributions to the fundamental knowledge on the regulation of a signal that is critical for cell viability and growth control. The significance of the second aim is that it will lead to the development of new transgenes which will serve as a model for investigations of the functional role of CK2 in the process of oncogenesis in the prostate, and in addition, may yield a novel model for study of the prostate tumor progression. The significance of the third aim relates to its potential for contributing new insights into a gene therapy approach for prostate cancer. In summary, these studies will provide fundamentally important new information on the mechanisms of CK2 functional activity as well as its implications in prostate tumor biology and a potential therapeutic target.