Abstract

It is the goal of this study to determine how tumor promoters and other growth promoting agents modulate hormone receptor action in order to understand the processes by which these agents influence all growth the major aim of the research proposed is to characterize the pathways and mechanisms by which nonTPA-type tumor promoters and nonPDGF-like components in the media from v-sis transformed cells alter epidermal growth factor (EGF) receptor properties. In particular, we will determine the effects of these agents on EGF receptor binding and phosphorylation, characterize the mechanism by which these agents modulate EGF receptor action, characterize the signal transduction pathways, and determine the biological relevance of these pathways. Both biochemical and molecular biological approaches will be used to accomplish these aims. An understanding of the factors involved in the regulation of signal-transducing receptors by tumor promoters and other growth promoting agents will provide valuable information regarding mechanisms controlling cell proliferation and transformation and their modulation by environmental factors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035541-07
Application #
3173131
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1987-09-01
Project End
1990-11-30
Budget Start
1989-08-01
Budget End
1990-11-30
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Chao, T S; Abe, M; Hershenson, M B et al. (1997) Src tyrosine kinase mediates stimulation of Raf-1 and mitogen-activated protein kinase by the tumor promoter thapsigargin. Cancer Res 57:3168-73
Xiong, W; Pestell, R G; Watanabe, G et al. (1997) Cyclin D1 is required for S phase traversal in bovine tracheal myocytes. Am J Physiol 272:L1205-10
Morrison, P; Saltiel, A R; Rosner, M R (1996) Role of mitogen-activated protein kinase kinase in regulation of the epidermal growth factor receptor by protein kinase C. J Biol Chem 271:12891-6
Morrison, P; Chung, K C; Rosner, M R (1996) Mutation of Di-leucine residues in the juxtamembrane region alters EGF receptor expression. Biochemistry 35:14618-24
Kuo, W L; Abe, M; Rhee, J et al. (1996) Raf, but not MEK or ERK, is sufficient for differentiation of hippocampal neuronal cells. Mol Cell Biol 16:1458-70
Kelleher, M D; Abe, M K; Chao, T S et al. (1995) Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis. Am J Physiol 268:L894-901
Hershenson, M B; Chao, T S; Abe, M K et al. (1995) Histamine antagonizes serotonin and growth factor-induced mitogen-activated protein kinase activation in bovine tracheal smooth muscle cells. J Biol Chem 270:19908-13
Englert, C; Hou, X; Maheswaran, S et al. (1995) WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. EMBO J 14:4662-75
Chao, T S; Foster, D A; Rapp, U R et al. (1994) Differential Raf requirement for activation of mitogen-activated protein kinase by growth factors, phorbol esters, and calcium. J Biol Chem 269:7337-41
Hou, X; Johnson, A C; Rosner, M R (1994) Identification of an epidermal growth factor receptor transcriptional repressor. J Biol Chem 269:4307-12

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