Abstract

We will continue our studies of the behavior of murine hematopoietic cells modified by acquired drug-resistance genes. We have recently cloned the gene for a mutant dihydrofolate reductase (DHFR) that is enzymatically active but highly resistant to inhibition by methotrexate (MTX) and certain other folic acid antagonists. We wish to test the effectiveness of the cloned gene in transforming mouse bone marrow cells to a state of MTX resistance. We plan to examine alternative strategies for modulating the transcription of the inserted drug-resistance gene sequences so that gene expression can be modified by the imposition of compounds such as glucocorticoids. We have developed a new technique for introducing macromolecules into mammalian cells and are exploring some of the variables associated with this methodology. (M)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA015619-13
Application #
3164231
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1977-06-01
Project End
1988-10-31
Budget Start
1987-07-01
Budget End
1988-10-31
Support Year
13
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Ahuja, H G; Foti, A; Zhou, D J et al. (1990) Analysis of proto-oncogenes in acute myeloid leukemia: loss of heterozygosity for the Ha-ras gene. Blood 75:819-22
Zhou, D J; Ahuja, H; Cline, M J (1989) Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease. Oncogene 4:105-8
Cline, M J (1989) Molecular diagnosis of human cancer. Lab Invest 61:368-80
Ahuja, H; Bar-Eli, M; Advani, S H et al. (1989) Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. Proc Natl Acad Sci U S A 86:6783-7
Cline, M J (1989) Oncogenes in hematologic neoplasia. Int J Cell Cloning 7:213-22
Ahuja, H G; Cline, M J (1988) Genetic and cytogenetic changes in acute lymphoblastic leukemia. Med Oncol Tumor Pharmacother 5:211-22
Cline, M J (1988) Oncogenes and the pathogenesis of human cancers: implications for cancer diagnosis and management. Br J Clin Pract Suppl 62:2-4
Masuda, H; Battifora, H; Yokota, J et al. (1987) Specificity of proto-oncogene amplification in human malignant diseases. Mol Biol Med 4:213-27
Meltzer, S J; Ahnen, D J; Battifora, H et al. (1987) Protooncogene abnormalities in colon cancers and adenomatous polyps. Gastroenterology 92:1174-80
Zhou, D; Battifora, H; Yokota, J et al. (1987) Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer. Cancer Res 47:6123-5

Showing the most recent 10 out of 19 publications