The discovery of viral oncogenes, c-onc, within acutely transforming retroviruses and their cellular homologues, c-onc, has provided a new perspective on the genetic basis of cancer. It is hoped that a complete understanding of the manner in which these genes may be abnormally expressed in the neoplastic cell will make clearer the molecular mechanism of transformation. The proposed research will investigate the postulated role of chromosomal translocations in causing the abnormal structure or expression of cellular oncogenes, We will study v-abl and c-myc oncogenes, whose cellular loci have both been found to be translocated in the human malignancies, chronic myelogenous leukemia and Burkitt's lymphoma, respectively. Fusions will be constructed in vitro between these two genes and the immunoglobulin heavy chain gene. By transfecting the constructs into cloned cell lines, we will attempt to determine the sequences necessary for the tissue-specific expression of these two oncogenes using normal and abnormal promoters. In addition, we will investigate the tissue-specific expression and possible tumorigenicity of these constructs by gene transfer into mice. In the last year of the proposed training period, we will attempt to clone and characterize the c-abl promoter and initiate studies on its functions in the normal cell.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA001074-03
Application #
3079565
Study Section
(SRC)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
076580745
City
Cambridge
State
MA
Country
United States
Zip Code
02142