NORMAL AND NEOPLASTIC PROSTATE

点击翻译按钮获取中文摘要

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.