The objective of this work is the characterization of the early stages of transformation induced in murine hematopoietic cells by different oncogenes. The culture system to be used are spleen-derived precursors of mast cells and of granulocyte-macrophages, both of which require WEHI-3 cell conditioned medium (WEHI-CM) for their growth. The following questions will be asked: 1. What effect do different oncogenes have on the proliferation and differentiation of mast cell and granulocyte-macrophage precursors? 2. Do oncogenes which complement each other in the transformation of fibroblasts also complement each other in the transformation of hematopoietic cells? 3. Which oncogenes or combination of oncogenes transform precursors of mast cells or granulocyte-macrophages into autocrine cells? The following properties of infected precursor cell populations will be studied: 1) their capacity to proliferate; 2) their potential to differentiate; 3) their dependence on WEHI-CM and IL-3; 4) their ability to produce growth factors; 5) their expression of proto-oncogenes and cellular genes, such as the Il-3 gene; 6) their karyotypes; 7) their in vivo tumorigenicity. A better understanding of the early (preleukemic) stages in the transformation of hematopoeitic cells may lead to methods suppressing the growth of transformed cells before they develop into autonomously growing, fully tumorigenic cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA013608-14
Application #
3163808
Study Section
Virology Study Section (VR)
Project Start
1978-05-01
Project End
1991-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
14
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Tran, Tram Anh; Kinch, Lisa; Peña-Llopis, Samuel et al. (2013) Platelet-derived growth factor/vascular endothelial growth factor receptor inactivation by sunitinib results in Tsc1/Tsc2-dependent inhibition of TORC1. Mol Cell Biol 33:3762-79
Kefas, Benjamin; Comeau, Laurey; Floyd, Desiree H et al. (2009) The neuronal microRNA miR-326 acts in a feedback loop with notch and has therapeutic potential against brain tumors. J Neurosci 29:15161-8
Vogt, M; Haggblom, C; Yeargin, J et al. (1998) Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts. Cell Growth Differ 9:139-46
Vogt, M; Haggblom, C; Swift, S (1989) Growth factor independence and indefinite growth (""immortalization"") appear simultaneously after crisis in murine myelocytes expressing v-myc. Oncogene Res 4:19-28
Bogenberger, J; Haas, M (1988) cDNA clones from autocrine thymic lymphoma cells encode two mitogenic proteins, a serine protease and a truncated T-cell receptor beta-chain. Oncogene Res 3:301-12
Vogt, M; Lesley, J; Bogenberger, J M et al. (1987) The induction of growth factor-independence in murine myelocytes by oncogenes results in monoclonal cell lines and is correlated with cell crisis and karyotypic instability. Oncogene Res 2:49-63
Vogt, M; Lesley, J; Bogenberger, J et al. (1986) Coinfection with viruses carrying the v-Ha-ras and v-myc oncogenes leads to growth factor independence by an indirect mechanism. Mol Cell Biol 6:3545-9
Vogt, M; Haggblom, C; Swift, S et al. (1986) Specific sequences of the env gene determine the host range of two XC-negative viruses of the Rauscher virus complex. Virology 154:420-4
Vogt, M; Haggblom, C; Swift, S et al. (1985) Envelope gene and long terminal repeat determine the different biological properties of Rauscher, Friend, and Moloney mink cell focus-inducing viruses. J Virol 55:184-92
Mally, M I; Vogt, M; Swift, S E et al. (1985) Oncogene expression in murine splenic T cells and in murine T-cell neoplasms. Virology 144:115-26