Two types of genes that participate directly in the development of malignancy ,ave been identified so far. Oncogenes are activated in tumor cells where they produce proteins whose function contributes to the malignant phenotype. In contrast, cancer suppressor genes are active in non-malignant cells where they apparently act to ensure normal growth and development, and their function is lost as cells become malignant. Experiments are proposed in this grant to make use of a line of tumorigenic hamster fibroblasts whose transformed phenotype is able to be suppressed by normal human fibroblasts in order to (1) clone the gene in the normal human genome able to control hamster cell transformation and then to test its ability to block the in vitro transformation and in vivo tumorigenicity of human tumor cell lines. (2) insert a dominant selectable genetic marker into the chromosome of the normal human fibroblast that is able to control hamster cell transformation (and on other chromosomes associated by cytogenetic data with tumor suppression) then to transfer the tagged chromosome singly to human tumor lines and test its efficacy in controlling transformation and tumorigenicity. To test the hypothesis that cancer suppressor genes act to block the activity and/or function of tumor oncogenes, hamster cells and hamster-human hybrids that either express or do not express the ability to suppress transformation will be tested for their susceptibility to and ability to regulate a subset of oncogenes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA027306-10
Application #
3167549
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1979-06-01
Project End
1993-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Dameron, K M; Volpert, O V; Tainsky, M A et al. (1994) The p53 tumor suppressor gene inhibits angiogenesis by stimulating the production of thrombospondin. Cold Spring Harb Symp Quant Biol 59:483-9
Klein, K G; Bouck, N P (1994) The distal region of the long arm of human chromosome 1 carries tumor suppressor activity for a human fibrosarcoma line. Cancer Genet Cytogenet 73:109-21
Tolsma, S S; Cohen, J D; Ehrlich, L S et al. (1993) Transformation of NIH/3T3 to anchorage independence by H-ras is accompanied by loss of suppressor activity. Exp Cell Res 205:232-9
Benton, B K; Volpert, O V; Bouck, N P (1993) Influence of a hamster tumor suppressor gene on transformation by viral and cellular oncogenes. Carcinogenesis 14:1209-14
Rastinejad, F; Polverini, P J; Bouck, N P (1989) Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56:345-55
Bouck, N P; Benton, B K (1989) Loss of cancer suppressors, a driving force in carcinogenesis. Chem Res Toxicol 2:1-11
Cohen, J D; Robins, H I; Mulcahy, R T et al. (1988) Interactions between hyperthermia and irradiation in two human lymphoblastic leukemia cell lines in vitro. Cancer Res 48:3576-80
Weitzman, S; Schmeichel, C; Turk, P et al. (1988) Phagocyte-mediated carcinogenesis: DNA from phagocyte-transformed C3H 10T1/2 cells can transform NIH/3T3 cells. Ann N Y Acad Sci 551:103-9;discussion 110
Tolsma, S S; Thomas, E; Bauer, K D et al. (1988) Genetic assessment of the strength of a cancer suppressor gene in hamster cells. Cancer Res 48:46-51
Bouck, N; Stoler, A; Polverini, P J (1986) Coordinate control of anchorage independence, actin cytoskeleton, and angiogenesis by human chromosome 1 in hamster-human hybrids. Cancer Res 46:5101-5

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