Abstract

The long-term goal of this research is to identify, at the molecular level, those gene products that are causally related to the ability of a cell to produce a tumor in an animal host. Using recombinant DNA technology and a panel of cell lines (with clonal variants) covering the range of tumorigenic potential from normal to highly tumorigenic, the genes uniquely or abundantly expressed in the tumorigenic cell lines will be cloned and characterized. A selected cDNA library from the tumorigenic cell line will be constructed and the genes governing tumorigenicity will be identified, their mRNAs characterized, and their protein products will be characterized and localized within the cell. An alternative approach is to microsequence surface antigens that have been identified only in the more tumorigenic cell lines. Once the sequence is known, oligonucleotide probes can be constructed to isolate the genes' coding for these products. We intend to identify and characterize those products that are involved in enhancing the tumorigenic potential of a transformed cell line, and to initiate studies of the regulation of those genes and the role that they play in the process of tumor formation in the host. (I)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA033434-03A1
Application #
3171309
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1982-08-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506

  Publications

Su, Z Z; Austin, V N; Zimmer, S G et al. (1993) Defining the critical gene expression changes associated with expression and suppression of the tumorigenic and metastatic phenotype in Ha-ras-transformed cloned rat embryo fibroblast cells. Oncogene 8:1211-9
Su, Z Z; Leon, J A; Jiang, H et al. (1993) Wild-type adenovirus type 5 transforming genes function as transdominant suppressors of oncogenesis in mutant adenovirus type 5 transformed rat embryo fibroblast cells. Cancer Res 53:1929-38
Brady-Kalnay, S M; Boghaert, E R; Zimmer, S et al. (1993) Increasing N-CAM-mediated cell-cell adhesion does not reduce invasion of RSV-transformed WC5 rat cerebellar cells. Clin Exp Metastasis 11:313-24
Nielsch, U; Pine, R; Zimmer, S G et al. (1992) Induced expression of the endogenous beta interferon gene in adenovirus type 5-transformed rat fibroblasts. J Virol 66:1884-90
Boylan, J F; Shih, T Y; Fisher, P B et al. (1992) Induction and progression of the transformed phenotype in cloned rat embryo fibroblast cells: studies employing type 5 adenovirus and wild-type and mutant Ha-ras oncogenes. Mol Carcinog 5:118-28
Su, Z Z; Olsson, C A; Zimmer, S G et al. (1992) Transfer of a dominant-acting tumor-inducing oncogene from human prostatic carcinoma cells to cloned rat embryo fibroblast cells by DNA-transfection. Anticancer Res 12:297-304
Nielsch, U; Zimmer, S G; Babiss, L E (1991) Changes in NF-kappa B and ISGF3 DNA binding activities are responsible for differences in MHC and beta-IFN gene expression in Ad5- versus Ad12-transformed cells. EMBO J 10:4169-75
Brady-Kalnay, S M; Boghaert, E R; Zimmer, S et al. (1991) Invasion by WC5 rat cerebellar cells is independent of RSV-induced changes in growth and adhesion. Int J Cancer 49:239-45
Boghaert, E R; Austin, V; Zimmer, S G (1991) The influence of the presence of adenovirus 5 E1a and E1b sequences on the pathology of rat embryonic fibroblasts transfected with activated c-Ha-ras and v-ras. Clin Exp Metastasis 9:231-43
Boylan, J F; Jackson, J; Steiner, M R et al. (1990) Role of the Ha-ras (RasH) oncogene in mediating progression of the tumor cell phenotype (review). Anticancer Res 10:717-24

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