The objective of this project is to determine basic mechanisms of how the transformed state is expressed phenotypically in terms of the regulation of cell proliferation and surface characteristics important to growth control The projects are designed to focus on the plasma membrane and cell surface as a major locus of growth control and site of expression of the transformed phenotype, not as an isolated series of events, but in the context of an integrated cellular system where provision is made for eventual contributions to understanding the exchange of information between the nucleus and the cell surface in the form of cell surface/cytoplasm and nucleus/cytoplasm interactions. The results of these studies are expected to advance our understanding of the control of cell proliferation and of the biochemical events critical to the expression of the transformed phenotype including altered growth rates, loss of adhesion, failures in contact inhibition mechanisms and acquisition of invasive potential. These studies will be explored in cellular systems common to all projects which make primary use of liver lines temperature sensitive for expression of the transformed phenotype. Experiments will be extended to cell-free systems as rapidly as they can be developed for examination of detailed mechanisms. In addition, we anticipate that the studies will add to the body of knowledge concerning events important to tumor induction, promotion, and progression and ultimately provide new biochemical targets for the development of strategies of chemoprevention or therapy of possible clinical importance. (A)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA036761-03S2
Application #
3093617
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1985-09-01
Project End
1989-06-30
Budget Start
1987-09-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Organized Research Units
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Low, H; Crane, F L; Grebing, C et al. (1991) Modification of transplasma membrane oxidoreduction by SV40 transformation of 3T3 cells. J Bioenerg Biomembr 23:903-17
Toole-Simms, W; Sun, I L; Morre, D J et al. (1990) Transplasma membrane electron and proton transport is inhibited by chloroquine. Biochem Int 21:761-9
Barr, R; Bottger, M; Crane, F L et al. (1990) Electron donation to the plasma membrane redox system of cultured carrot cells stimulates proton release. Biochim Biophys Acta 1017:91-5
Paulik, M; Nowack, D D; Morre, D J (1988) Isolation of a vesicular intermediate in the cell-free transfer of membrane from transitional elements of the endoplasmic reticulum to Golgi apparatus cisternae of rat liver. J Biol Chem 263:17738-48
Jacobsen, L B; Putnam, J E; Sawick, D P et al. (1988) Pyrimidine nucleosides enhance the efficacy of inhibitors of pyrimidine biosynthesis in cultured hepatocellular carcinoma cells. Life Sci 42:913-8
Verlander, J W; Madsen, K M; Low, P S et al. (1988) Immunocytochemical localization of band 3 protein in the rat collecting duct. Am J Physiol 255:F115-25
Sun, I L; Toole-Simms, W; Crane, F L et al. (1988) Transformation with SV40 virus prevents retinoic acid inhibition of plasma membrane NADH diferric transferrin reductase in rat liver cells. J Bioenerg Biomembr 20:383-91
Weyman, C M; Taparowsky, E J; Wolfson, M et al. (1988) Partial down-regulation of protein kinase C in C3H 10T 1/2 mouse fibroblasts transfected with the human Ha-ras oncogene. Cancer Res 48:6535-41
Kraft, A S; Reeves, J A; Ashendel, C L (1988) Differing modulation of protein kinase C by bryostatin 1 and phorbol esters in JB6 mouse epidermal cells. J Biol Chem 263:8437-42
Williams, J S; Eckdahl, T T; Anderson, J N (1988) Bent DNA functions as a replication enhancer in Saccharomyces cerevisiae. Mol Cell Biol 8:2763-9

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