The first goal is to determine which of the oncogenes we have found to be expressed in B cell neoplasms are capable, either individually or in pairs, of neutralizing normal cell cycle restriction points controlling B lymphocyte growth. The second goal is to address the need for cloned normal B cells in sufficient quantity to study in molecular detail the events of B cells activation (growth and differentiation) and inactivation (tolerance and suppression). The lack of such populations has to date hindered progress in the study of B cell growth and differentiation factors, the receptors for these factors and their mechanisms of action. In comparison, the availability of non-transformed antigen-specific helper T cell clones and cytotoxic T cell clones have made the detailed study of these parameters in the T cell lineage possible. The current status of the biochemistry of B cell activation and inactivation demonstrates the need for such a system. Our focus with the cloned B cell populations we generate will be to pursue our studies on the regulation of B cell growth. Both of these goals will be addressed using hybrid genes constructed with the micro-enhancer to ensure expression of the promoter-linked genes in B cells and a regulatable promoter controlling the expression of an oncogene. Removal of the agent used to activate the promoter should shut down synthesis of the oncogene product providing a conditionally """"""""normal"""""""" cell population which will allow the study of parameters involved in B cell growth. The advantages of the inducible oncogene are several. A large number of cells may be grown while the promoter is induced, thus generating as many cells as needed for biochemical and molecular genetic experiments. In addition, a direct comparison of normal growth with transformed growth parameters may be performed using the same clonal population of cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA045054-02
Application #
3188051
Study Section
Immunobiology Study Section (IMB)
Project Start
1988-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
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
DeCino, P; Lernhardt, W; Herbst, H et al. (1988) Expression of oncogenes in normal and transformed murine B lymphocytes. Oncogene Res 3:33-7