The goal of the proposed research is an understanding of neoplastic transformation through the study of viral and cellular onc genes and of the oncogenic phenotype. We will identify new onc genes using newly isolated, rapidly transforming retroviruses and will define their place and function in the network of cellular regulatory genes. The new onc genes will be characterized by determining their nucleotide sequence and isolating the corresponding protein product. The structure and expression of homologous cellular loci will be studied. Investigations of function will concentrate on the properties of the new onc proteins and on sequence comparisons with known cellular genes. We will also search for a system in which cellular sequences are acquired by a retrovirus genome with a frequency high enough to allow mechanistic analysis. Specific cellular functions and targets in the process of oncogenic transformation will be searched for and identified by cell mutants that are temperature-sensitive for the transformed phenotype. In a different approach to this same question, differentiated cell types that are refractory to the action of an expressed onc gene will be studied. We also plan to analyze stage-specific differentiation markers in the course of virus induced leukemia and relate changes in the expression of these markers to onc gene action. In an effort to explain the origin of spontaneous nonviral tumors, we will look for activated onc genes in tumors and tumor cell lines that are free of rapidly transforming retroviruses. All these investigations will contribute to our knowledge of molecular mechanisms regulating cell growth and differentiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA042564-05
Application #
3479427
Study Section
Special Emphasis Panel (SRC)
Project Start
1986-06-01
Project End
1993-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Harada, Josephine N; Bower, Kristen E; Orth, Anthony P et al. (2005) Identification of novel mammalian growth regulatory factors by genome-scale quantitative image analysis. Genome Res 15:1136-44
Nishizawa, Makoto; Fu, Shu-Ling; Kataoka, Kohsuke et al. (2003) Artificial oncoproteins: modified versions of the yeast bZip protein GCN4 induce cellular transformation. Oncogene 22:7931-41
Nishizawa, Makoto; Kataoka, Kohsuke; Vogt, Peter K (2003) MafA has strong cell transforming ability but is a weak transactivator. Oncogene 22:7882-90
Jiang, B H; Jiang, G; Zheng, J Z et al. (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12:363-9
Aoki, M; Blazek, E; Vogt, P K (2001) A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc Natl Acad Sci U S A 98:136-41
Maslyar, D J; Aoki, M; Vogt, P K (2001) The growth-promoting activity of the Bad protein in chicken embryo fibroblasts requires binding to protein 14-3-3. Oncogene 20:5087-92
Mende, I; Malstrom, S; Tsichlis, P N et al. (2001) Oncogenic transformation induced by membrane-targeted Akt2 and Akt3. Oncogene 20:4419-23
Cohen, S B; Waha, A; Gelman, I H et al. (2001) Expression of a down-regulated target, SSeCKS, reverses v-Jun-induced transformation of 10T1/2 murine fibroblasts. Oncogene 20:141-6
Jiang, B H; Zheng, J Z; Aoki, M et al. (2000) Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci U S A 97:1749-53
Xia, Y; Zhang, Z; Kruse, U et al. (2000) The new serine-threonine kinase, Qik, is a target of the Qin oncogene. Biochem Biophys Res Commun 276:564-70

Showing the most recent 10 out of 76 publications