REGULATION OF CYTOKINE MRNA STABILITY IN TUMOR CELLS

Project: Research project

Description

This application proposes to study the role of cytokines in tumor growth
and the factors responsible for cytokine mRNA stability in tumor cells.
Cytokine mRNAs are unusually stable in cultured tumor cells and tumor
xenografts in mice. Specific aims: 1) To determine the physiological
implications of stable cytokine mRNAs in tumor cells using recombinant
cytokines, anticytokine antibodies and antisense DNA. 2) To study the
factors which control mRNA stability using similar techniques and
focusing on the role of cytokines such as IL-1, TGFb, TNF, GM-CSF, IL-6.
3) To study the mechanism of stabilization of cytokine mRNA in tumors
using RNA gel retardation, footprinting, and in vitro polysome systems
to look for possible RNA binding proteins and to determine the
structural sequences important in stability. 4) To study the production
of factors which regulate RNA stability using protein biochemistry and
the polysome system. Phase I of this project will be devoted to
completing specific aims 1&2 and mastering RNA gel retardation and
footprinting. Phase II will apply the techniques learned in Phase I to
the identification and isolation of an RNA binding protein and
identification of factors responsible for RNA stability. Phase II will
also attempt to confirm the results obtained for cultured cells and
xenografts by examining fresh tumor specimens. Long term goals include
isolating and sequencing the binding protein which would enable cloning
of its gene and a detailed study of its regulation. It has been
suggested that cytokines may play a role in tumor growth perhaps via
autocrine stimulation or via other mechanisms. An understanding of the
increased stability of cytokine mRNA in tumor cells may lead to the
ability to control cytokine levels in these cells and a therapeutic
approach to controlling tumor growth in cancer patients.
StatusFinished
Effective start/end date9/30/919/29/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Cytokines
RNA Stability
Neoplasms
RNA-Binding Proteins
Polyribosomes
Messenger RNA
Antisense DNA
Gels
RNA
Cultured Tumor Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Growth
Interleukin-1
Biochemistry
Cultured Cells
Carrier Proteins
Antibodies
Genes
Proteins
Heterografts

ASJC

  • Medicine(all)