Cell proliferation in higher eukaryotes is a tightly regulated process that is largely governed by extracellular factors. These include hormones, growth factors, growth inhibitors and the cellular microenvironment, for example, the proximity of neighboring cells. Tumorigenic cells exhibit faulty or unregulated growth control, and they often fail to heed one or more of the environmental signals that limit the proliferation of normal cells. There is substantial evidence that growth-controlling environment signals have acute effects upon the expression of specific genes that are though important for the proliferative response. This proposal examines the biochemical mechanisms by which environmental signals alter the expression of certain genes in nontumorigenic murine fibroblasts, in tumorigenic derivatives derived by chemical or viral transformation, and in transfected derivatives bearing one or more known genetic change. The experiments will determine the intracellular pathways by which some environmental factors induce or suppress the transcription, mRNA accumulation or translation of certain growth-related genes, the role of certain protein kinases and other regulatory proteins in mediating changes in gene expression and the proliferative response, and they will explore the function of some of the genes in regulating proliferation. These studies will provide an important biochemical and molecular biological base for understanding the interactions between environmental signals and specific gene expression in the regulation of normal and tumor cell growth.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010004-07
Application #
2051262
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1987-09-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Anatomy/Cell Biology
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
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Oshima, J; Steinmann, K E; Campisi, J et al. (1993) Modulation of cell growth, p34cdc2 and cyclin A levels by SV-40 large T antigen. Oncogene 8:2987-93