Research My research interest is in the area of cell communication in cancer cells. Cancer cells exhibit many defects in cell-cell communications that contribute to the loss of cell stability (excess cell growth). One type of cell-cell communications is through gap junctions. Gap junctions are composed of channels that permit the passage of ions and low molecular weight metabolites. Stable abnormal regulation of gap junction function has been associated with the activation of several oncogenes. Several tumor suppressor genes have also been associated with the up-regulation of gap junction function. Gap junctions are controlled through C-terminal phosphorylation of connexin by many kinases, including protein kinase C (PKC). Our research is focusing on the role of PKC in the regulation of gap junction activity in colon cancer cells. We use the tools of molecular biology, tissue culture, animal models, and synthetic peptides. We have shown that these synthetic peptides can be a potential treatment of colon cancer. Understanding how gap junctions are controlled in colon cancer cells may find the key players in regulating cancer cells. Selected publications T. A. Nguyen, L.J. Takemoto, and D.J. Takemoto. Inhibition of gap junction activity through the release of the C1B domain of PKCg from 14-3-3: Identification of PKCg binding sites. (2004) J. Biol. Chem. in press, Sep 2004; 10.1074/jbc.M403040200. T. A. Nguyen, D. Boyle, L.M. Wagner, T. Shinohara, and D.J. Takemoto. LEDGF Activation of PKC g and Gap Junction Disassembly in Lens Epithelial Cells. (2003) Experimental Eye Research 76, 565-572. C. Qin, T. Nguyen, J. Stewart, I. Samudio, R. Burghardt, and S. Safe. Estrogen Up-Regulation of p53 Gene Expression in MCF-7 Breast Cancer Cells Is Mediated by Calmodulin Kinase IV-Dependent Activation of a Nuclear Factor kappaB/CCAAT-Binding Transcription Factor-1 Complex. (2002) Mol Endocrinol. 16, 1793-1809. Matthew Stoner, Fan Wang, Mark Wormke, Thu Nguyen, Ismael Samudio, Carrie Vyhlidal, Dieter Marme, Gunter Finkenzeller, and Stephen Safe. Inhibition of Vascular Endothelial Growth Factor Expression in HEC1A Endometrial Cancer Cells through Interactions of Estrogen Receptor a and Sp3 Proteins. (2000) J. Biol. Chem. 275, 22769-22779. Brad Saville, Mark Wormke, Fan Wang, Thu Nguyen, Eva Enmark, George Kuiper, Jan-Ake Gustafsson, and Stephen Safe. Ligand-, Cell-, and Estrogen Receptor Subtype (a/b)-dependent Activation at GC-rich (Sp1) Promoter Elements. (2000) J. Biol. Chem. 275, 5379-5387. Thu Nguyen, Debie Hoivik, Jeong-Eun, and Stephen Safe. Interactions of Nuclear Receptor Coativator/Corepressor Proteins with the Aryl Hydrocarbon Receptor Complex. (1999) Archives of Biochemistry and Biophysics. 367, 250-257. |
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