Over the years, we have focused on investigation of the fundamental functional biology of protein kinase CK2 with a specific view to its role in the pathobiology of prostate cancer. CK2 is a ubiquitous highly conserved multifunctional protein ser/thr kinase that has long been implicated in cell growth and proliferation. Its importance in cancer is emphasized by its deregulation in all the cancers that have been examined, including prostate cancer. Our paradigm-shifting discovery that CK2 can also suppress apoptosis suggests, for the first time, an important new link between CK2 and oncogenesis since deregulation of apoptosis (especially in prostate cancer) is a key feature of cancer phenotype. Our working hypothesis is that CK2 plays crucial roles in normal and abnormal prostatic growth control, and its deregulation is critically associated with oncogenesis through its impact on cell growth, apoptosis, and survival. Our long-term goals are to investigate the mechanisms involved in CK2 signaling in cell growth and suppression of apoptosis, and to exploit the key features of CK2 functional pathobiology in translational studies targeted to prostate cancer. To this end, we propose (a) to investigate the mechanisms involved in shuttling of CK2 to the nuclear matrix; (b) to examine the mechanisms by which CK2 suppresses apoptosis; (c), to exploit its downregulation as a potential therapeutic modality; and (d) to target its overexpression for generating a new transgenic mouse model of prostate cancer. In summary, our studies on CK2 functional biology with reference to prostate cancer biology represent an important and unique area of investigation. Also significant is the application of this knowledge to the development of a new transgenic mouse model and a new therapeutic modality for prostate cancer. The relevance of these studies is underscored by the fact that prostate cancer is a leading cause of cancer-related deaths in men in the U.S.A.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA015062-31
Application #
7117612
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Ault, Grace S
Project Start
1976-12-01
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
31
Fiscal Year
2006
Total Cost
$221,470
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Kramerov, A A; Ahmed, K; Ljubimov, A V (2012) Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alterations. J Cell Biochem 113:2948-56
Trembley, Janeen H; Unger, Gretchen M; Korman, Vicci L et al. (2012) Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells. Cancer Lett 315:48-58
Kramerov, A A; Golub, A G; Bdzhola, V G et al. (2011) Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Mol Cell Biochem 349:125-37
Trembley, Janeen H; Unger, Gretchen M; Tobolt, Diane K et al. (2011) Systemic administration of antisense oligonucleotides simultaneously targeting CK2? and ?' subunits reduces orthotopic xenograft prostate tumors in mice. Mol Cell Biochem 356:21-35
Brown, Matthew S; Diallo, Oumou T; Hu, Michael et al. (2010) CK2 modulation of NF-kappaB, TP53, and the malignant phenotype in head and neck cancer by anti-CK2 oligonucleotides in vitro or in vivo via sub-50-nm nanocapsules. Clin Cancer Res 16:2295-307
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
Trembley, Janeen H; Chen, Zhong; Unger, Gretchen et al. (2010) Emergence of protein kinase CK2 as a key target in cancer therapy. Biofactors 36:187-95
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

Showing the most recent 10 out of 69 publications