The recently identified piscine retroviruses and their associate neoplasia will provide new model systems for the investigation of molecular mechanisms of oncogenesis. Walleye dermal sarcoma virus (WDSV) is associated with tumors that develop and regress on a seasonal basis. Therefore, WDSV offers the unique opportunity to study the mechanisms of tumor regression. WDSV is the first example of an acutely transforming, complex retrovirus, which encodes an accessory protein retroviral cyclin (rv-cyclin) with homology to cellular D-type cyclins. Cyclin D1 is an oncogene that is amplified and over-expressed in several humor tumors. The long term objectives of this research are to characterize cellular proteins with unknown function that directly interact with the rv-cyclin and to identify compounds that alter these interactions. We will first determine the subcellular localization of the interacting cellular proteins. Further characterization of these proteins will be done by quantitating the levels of proteins and their transcripts in different cell types and tissues and during development. A fluorescence assay and a counter selection yeast two-hybrid system will be used to screen for compounds that interfere with the binding of rv-cyclin and its interacting cellular proteins. In vitro kinase assays will be used to identify compounds that affect the function of the rv-cyclin/CDK complex. Finally, compounds found to alter the interaction of cellular proteins with WDSV rv-cyclin will be evaluated for their inhibitory effect on immortalization and transformation of primary cells.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015563-03
Application #
6652876
Study Section
Special Emphasis Panel (ZRR1)
Project Start
2002-09-01
Project End
2003-08-31
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Subramanian, Chitra; Grogan, Patrick T; Opipari, Valerie P et al. (2018) Novel natural withanolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-?B activation. Oncotarget 9:14509-14523
Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro et al. (2018) Co-treatment with a C1B5 peptide of protein kinase C? and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation. Biochem Biophys Res Commun 495:962-968
He, Chenchen; Duan, Shaofeng; Dong, Liang et al. (2017) Characterization of a novel p110?-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate 77:1187-1198
White, Peter T; Subramanian, Chitra; Zhu, Qing et al. (2016) Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery 159:142-51
Ohta, Naomi; Ishiguro, Susumu; Kawabata, Atsushi et al. (2015) Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One 10:e0123756
Li, Benyi; Thrasher, James Brantley; Terranova, Paul (2015) Glycogen synthase kinase-3: a potential preventive target for prostate cancer management. Urol Oncol 33:456-63
Ishiguro, Susumu; Yoshimura, Kiyoshi; Tsunedomi, Ryouichi et al. (2015) Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice. Cancer Biol Ther 16:307-16
Li, Benyi; Sun, Aijing; Jiang, Wencong et al. (2014) PI-3 kinase p110?: a therapeutic target in advanced prostate cancers. Am J Clin Exp Urol 2:188-98
Bibis, Stergios S; Dahlstrom, Kelly; Zhu, Tongtong et al. (2014) Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs. Mol Biochem Parasitol 196:90-9
Subramanian, Chitra; Zhang, Huaping; Gallagher, Robert et al. (2014) Withanolides are potent novel targeted therapeutic agents against adrenocortical carcinomas. World J Surg 38:1343-52

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