Project Details


This research is an investigation of some of the biochemical processes
involved in malignant cell differentiation. The case under consideration
is the differentiation of mouse neuroblastoma cells in tissue culture. The
differentiation inducer to be studied is cyclic adenosine
3':5'-monophosphate (cAMP). The immediate goals of this research are to:
(1) determine the role of cAMP-dependent protein kinase as an effector of
cAMP action in neuroblastoma differentiation; (2)\study the mechanism of
the increased expression of R I , a free cAMP-binding protein, and its
functonal significance in neuroblastoma cell differentiation. Our
approaches to define the action of cAMP-dependent protein kinase in
neuroblastoma cell differentiation include: (a)\to screen/select, isolate,
and characterize protein kinase-minus mutants of the neuroblastoma cells
and to use these mutants to relate the occurence of cAMP-dependent protein
kinase with the cells' sensitivity towards cAMP; (b)\the use of small
unilamellar liposomes to deliver cyclic nucleotides intracellularly to
examine the occupancy of cAMP-receptor protein, the activation of
cAMP-dependent protein kinase, and the evocation of cAMP-regulated
biological processes in intact neuroblastoma cells; (c) the use of
microinjection techniques to introduce purified cAMP-dependent protein
kinase or an inhibitor of the kinase into intact neuroblastoma cells, to
demonstrate that the expression of various differentiated functions in
these cells is causally related to the activity of cAMP-dependent protein
kinase in these cells. In order to gain a better understanding of the
mechanism that underlies the increased experssion of the R I cAMP-binding
protein during neuroblastoma cell differentiation, we will study the rate
of synthesis and degradation of this protein and quantitate the level of
mRNA coding for this protein during the course of differentiation. (M)
Effective start/end date9/1/858/31/89


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


  • Medicine(all)

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