Project: Research project

Project Details


The overall objective is to understand the mechanisms by which activated
proto-oncogenes alter normal growth regulatory processes. This will be
accomplished by the use of both molecular (i.e. Northern hybridizations and
nuclear run-off assays) and cell biological technique (i.e. growth factor
requirements for G1 traverse and logarithmic growth.

C3H/10t1/2 cells are not stimulated to grow in soft agar by addition of
TGFBeta. We have obtained preliminary data demonstrating that transfection
of C3H/10T1/2 cells with a mouse c-myc gene linked to an SV40 promoter
results in responsiveness to TGFBeta as assayed by colony formation in soft
agar. In addition, transfection with an activated H-ras gene results in a
transformed cellular morphology, spontaneous growth in soft agar and
markedly decreased binding of 125I-labeled TGFBeta.

It is proposed that transfection with the activated H-ras gene abrogated
proliferative restraints by inappropriate transcriptional and translational
activity in growth factor or cell cycle regulated genes normally utilized
during controlled proliferation. The myc gene, however, is suggested to be
a modulator, rather than inducer of various growth promoting signals.
Thus, an optimal (not necessarily appropriate) growth response will result
from the synergistic action of both proto-oncogenes. These hypotheses will
be addressed by the following specific aims: 1) Determining whether
C3H/10T1/2 cells transfected with an activated H-ras and/or myc gene show
transcriptional activity of genes known to be under growth factor control;
2) Determining the effects of ras and/or myc gene transfection in
C3H/10T1/2 cells on the in vitro production of specific growth factors; 3)
Determining the growth factor requirements for G1 traverse and logarithmic
growth of ras and/or myc gene transfected cells; and 4) Further
characterization of the growth factor specificity for anchorage-independent
growth of myc gene transfected C3H/10T1/2 cells.

Overall, these studies should increase our knowledge of the mechanisms
controlling normal cellular proliferation as well as transformation.
Effective start/end date9/1/866/30/94


  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Institutes of Health
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute


  • Medicine(all)


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