This proposal pertains to studies on two aspects of neoplastic transformation of cells in tissue culture by polyoma virus. One set of experiments deals with the understanding of the steps leading to the integration of the viral DNA into the host genome and the role of large T-antigen in this progess. Specifically, we will ask whether viral genomes are converted to high molecular weight concatamers after infection, whether recombination plays a role in the conversion, and, if so, whether the integrated viral molecules are selectively of recombinant nature and whether recombination is restricted to one area of the viral genome. Whereas most studies will be carried out with Fischer rat cells, rat NRK and hamster BHK will be used to compare the role of various hosts in some aspects of the integration process. The other set of experiments consists of comparative molecular studies on two groups of cells transformed by ts-a mutants, those with temperature sensitive and those with temperature insensitive transformed phenotype. The experiments will test the following points: 1) whether the temperature sensitive phenotype and insensitive phenotypes can be transferred to recipient cells by DNA transfections, 2) how a ts phenotype can evolve to a non-ts one, and 3) whether the expression of viral T-antigens is cell cycle dependent in temperature sensitive clones.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029270-05
Application #
3168621
Study Section
Virology Study Section (VR)
Project Start
1981-01-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Osteopathy
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Fluck, Michele M; Schaffhausen, Brian S (2009) Lessons in signaling and tumorigenesis from polyomavirus middle T antigen. Microbiol Mol Biol Rev 73:542-63, Table of Contents
Cheng, Jingwei; DeCaprio, James A; Fluck, Michele M et al. (2009) Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens. Semin Cancer Biol 19:218-28
Chen, Li; Wang, Xiaoyu; Fluck, Michele M (2006) Independent contributions of polyomavirus middle T and small T to the regulation of early and late gene expression and DNA replication. J Virol 80:7295-307
Spink, Kathryn M; Fluck, Michele M (2003) Polyomavirus hr-t mutant-specific induction of a G2/M cell-cycle arrest that is not overcome by the expression of middle T and/or small T. Virology 307:191-203
Chen, L; Fluck, M (2001) Kinetic analysis of the steps of the polyomavirus lytic cycle. J Virol 75:8368-79
Chen, L; Fluck, M M (2001) Role of middle T-small T in the lytic cycle of polyomavirus: control of the early-to-late transcriptional switch and viral DNA replication. J Virol 75:8380-9
Syu, L J; Fluck, M M (1997) Site-specific in situ amplification of the integrated polyomavirus genome: a case for a context-specific over-replication model of gene amplification. J Mol Biol 271:76-99
Fluck, M M; Haslam, S Z (1996) Mammary tumors induced by polyomavirus. Breast Cancer Res Treat 39:45-56
Chen, M C; Redenius, D; Osati-Ashtiani, F et al. (1995) Enhancer-mediated role for polyomavirus middle T/small T in DNA replication. J Virol 69:326-33
Chen, H H; Fluck, M M (1993) Cell cycle control of polyomavirus-induced transformation. J Virol 67:1996-2005

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