The long range goal of these studies is to prepare efficient and stable tools for the transfer of foreign genes into tumor cells to study the mechanism of action of tumor suppressor genes and to develop approaches to gene therapy for some kinds of tumors. We wish to use the models of the retinoblastoma (Rb) and p53 genes to examine the effect of expression of wild type and mutant forms of these tumor suppressor genes on cell phenotype. We wish also to determine the mechanism and clinical usefulness of changes in growth and tumorigenicity properties of cells in which the expression of these genes is restored by viral vector gene transfer.
Our specific aims are: 1. to modify and improve Moloney murine leukemia virus (MoMLV)-based vectors, 2. to develop an alternative retroviral vector, based on simian sarcoma- associated virus (SSAV), 3. determine the phenotypic effect of restored Rb expression on tumor cell phenotype, 4. develop alternative gene transfer tools, including adeno-associated virus (AAV) and liposomes, 5. study the feasibility of in vivo suppression of existing tumors by efficient delivery in vivo of the Rb tumor suppressor gene, 6. to extend the Rb suppression to a variety of cells in which defects of p53 are associated with the tumor phenotype.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (SRC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
Zip Code
Runnebaum, I B; Yee, J K; Kieback, D G et al. (1994) Wild-type p53 suppresses the malignant phenotype in breast cancer cells containing mutant p53 alleles. Anticancer Res 14:1137-44
Yee, J K; Friedmann, T; Burns, J C (1994) Generation of high-titer pseudotyped retroviral vectors with very broad host range. Methods Cell Biol 43 Pt A:99-112
Yee, J K; Miyanohara, A; LaPorte, P et al. (1994) A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes. Proc Natl Acad Sci U S A 91:9564-8
Burns, J C; Friedmann, T; Driever, W et al. (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci U S A 90:8033-7
Roemer, K; Friedmann, T (1993) Modulation of cell proliferation and gene expression by a p53-estrogen receptor hybrid protein. Proc Natl Acad Sci U S A 90:9252-6
Roemer, K; Friedmann, T (1992) Concepts and strategies for human gene therapy. Eur J Biochem 208:211-25