NORMAL AND NEOPLASTIC PROSTATE

蛋白质磷酸化是一个重要的机制，在控制 细胞功能，包括基因组调控和细胞增殖。 因此，研究蛋白激酶系统在适当 实验模型是当前非常感兴趣的。由于多种 多年来，该实验室一直专注于蛋白激酶CK 2，因为它涉及 前列腺生长控制。 CK 2是一种多能信使 独立Ser/Thr激酶。大量证据表明， 在控制正常细胞生长和增殖中的作用。 谦虚 其活性的失调也与异常生长有关， 研究表明它参与了致癌过程。 我们的工作 前列腺中的CK 2与这些结论一致。 因此，我们的校长 这项正在进行的研究的假设是，蛋白激酶CK 2发挥作用， 在前列腺生长控制及其失调中的基本作用是 与前列腺肿瘤有关。本文件提出的具体目标 更新申请源于对CK 2生物学的了解， 正常和肿瘤性生长，代表逻辑进展， 扩大正在进行的研究。 第一个目标是继续调查所涉机制 在CK 2功能的生物化学/生物学方面， 前列腺生长，并分析CK 2在前列腺癌中的NM状态 与格里森等级有关。 第二个目标是利用CK 2 信号在转基因模型中研究其参与的机制， 致癌过程 第三个目标是将CK 2信号作为目标， 干扰前列腺生长的潜在位点。 第一个目标的重要性在于它对社会发展的贡献。 关于信号调节的基本知识， 细胞活力和生长控制。 第二个目标的意义 它将导致新的转基因的发展， 作为一个模型，研究CK 2的功能作用， 前列腺中的肿瘤发生过程，此外，可能产生 研究前列腺肿瘤进展的新模型。 的 第三个目标的重要性在于它有可能促进 前列腺癌基因治疗方法的新见解。 总之，这些研究将提供重要的新的 关于CK 2功能活性机制及其 前列腺肿瘤生物学的意义和潜在的治疗 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.