Abstract

The goal of this program is to understand cellular transformation at the molecular level: both the genetic events which induce transformation and the alteration in biochemical events which ensue. There are five component sections: Human Oncogenes (Wigler) focuses on new human oncogenes which have either a novel structure or an interesting pattern of expression in neoplasia. Oncogenesis in Transgenic Mice (Hanahan and Field) utilizes a relatively new technology to explore the multistep nature of carcinogenesis in specific tissues. c-fos Transcriptional Activation (Gilman) explores the molecules which induce fos oncogene expression in response to signal transduction. Tropomyosins and Transformation (Helfman) analyses changes in the expression of the tropomyosin isoforms and their effects on the transformed phenotype. Membrane Signal Transduction (Feramisco and Bar-Sagi) describes the interactions of various second messenger systems related to growth proliferation signals which originate at the cellular membrane. The project brings together five diverse approaches to a common problem.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA046370-02
Application #
3094199
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1988-03-01
Project End
1993-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724

  Publications

Chardin, P; Camonis, J H; Gale, N W et al. (1993) Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science 260:1338-43
Bar-Sagi, D; Rotin, D; Batzer, A et al. (1993) SH3 domains direct cellular localization of signaling molecules. Cell 74:83-91
Lees-Miller, J P; Henry, G; Helfman, D M (1992) Identification of act2, an essential gene in the fission yeast Schizosaccharomyces pombe that encodes a protein related to actin. Proc Natl Acad Sci U S A 89:80-3
Pittenger, M F; Helfman, D M (1992) In vitro and in vivo characterization of four fibroblast tropomyosins produced in bacteria: TM-2, TM-3, TM-5a, and TM-5b are co-localized in interphase fibroblasts. J Cell Biol 118:841-58
Bar-Sagi, D (1992) Mechanisms of signal transduction by Ras. Semin Cell Biol 3:93-8
Attar, R M; Gilman, M Z (1992) Expression cloning of a novel zinc finger protein that binds to the c-fos serum response element. Mol Cell Biol 12:2432-43
Mulligan, G J; Guo, W; Wormsley, S et al. (1992) Polypyrimidine tract binding protein interacts with sequences involved in alternative splicing of beta-tropomyosin pre-mRNA. J Biol Chem 267:25480-7
Lanson Jr, N A; Glembotski, C C; Steinhelper, M E et al. (1992) Gene expression and atrial natriuretic factor processing and secretion in cultured AT-1 cardiac myocytes. Circulation 85:1835-41
Lowenstein, E J; Daly, R J; Batzer, A G et al. (1992) The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70:431-42
Goodwin, L O; Lees-Miller, J P; Leonard, M A et al. (1991) Four fibroblast tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene via alternative RNA splicing and the use of two promoters. J Biol Chem 266:8408-15

Showing the most recent 10 out of 28 publications