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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA015062-28
Application #
6512520
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Ault, Grace S
Project Start
1976-12-01
Project End
2004-08-31
Budget Start
2002-06-01
Budget End
2004-08-31
Support Year
28
Fiscal Year
2002
Total Cost
$207,847
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Wang, Guixia; Pan, Yunqian; Ahmad, Kashif A et al. (2010) Protein B23/nucleophosmin/numatrin nuclear dynamics in relation to protein kinase CK2 and apoptotic activity in prostate cells. Biochemistry 49:3842-52
Hanif, Ismail M; Ahmad, Kashif A; Ahmed, Khalil et al. (2009) Involvement of reactive oxygen species in apoptosis induced by pharmacological inhibition of protein kinase CK2. Ann N Y Acad Sci 1171:591-9
Trembley, J H; Wang, G; Unger, G et al. (2009) Protein kinase CK2 in health and disease: CK2: a key player in cancer biology. Cell Mol Life Sci 66:1858-67
McDonnell, Maureen A; Abedin, Md Joynal; Melendez, Manuel et al. (2008) Phosphorylation of murine caspase-9 by the protein kinase casein kinase 2 regulates its cleavage by caspase-8. J Biol Chem 283:20149-58
Ahmad, Kashif A; Wang, Guixia; Unger, Gretchen et al. (2008) Protein kinase CK2--a key suppressor of apoptosis. Adv Enzyme Regul 48:179-87
Wang, Guixia; Ahmad, Kashif A; Harris, Nathan H et al. (2008) Impact of protein kinase CK2 on inhibitor of apoptosis proteins in prostate cancer cells. Mol Cell Biochem 316:91-7
Ahmad, Kashif A; Harris, Nathan H; Johnson, Andrew D et al. (2007) Protein kinase CK2 modulates apoptosis induced by resveratrol and epigallocatechin-3-gallate in prostate cancer cells. Mol Cancer Ther 6:1006-12
He, Hongbin; Tan, Mingjia; Pamarthy, Deepika et al. (2007) CK2 phosphorylation of SAG at Thr10 regulates SAG stability, but not its E3 ligase activity. Mol Cell Biochem 295:179-88
Wang, Guixia; Ahmad, Kashif A; Ahmed, Khalil (2006) Role of protein kinase CK2 in the regulation of tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis in prostate cancer cells. Cancer Res 66:2242-9
Wang, Guixia; Ahmad, Kashif A; Unger, Gretchen et al. (2006) CK2 signaling in androgen-dependent and -independent prostate cancer. J Cell Biochem 99:382-91

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