ABERRANT GENE REGULATION INDUCED BY V FOS TRANSFORMATION

Project Details

Description

Recent studies have shown that a number of nuclear oncogenes, including
fos, encode nuclear proteins that function as trans-acting transcriptional
factors. Previous studies showed that expression of a mutant v-fos protein
or overexpression of the c-fos proto-oncogene can both lead to cell
transformation. Controlled expression of the c-fos protein however, does
not lead to malignancy. It is thus likely that only a small subset of all
the genes sensitive to regulation by Fos oncogenes actually contribute to
induction of a transformed phenotype. This proposal outlines experiments
designed to identify and study the regulation of genes whose expression is
altered specifically in response to transformation of cells by the Fos
oncogenes. A comparison of gene expression in v-fos transformation cells
and in revertant clones isolated from the former has already lead to the
identification of such genes. These genes encode alpha1 (I) and alpha2 (I)
procollagen, two major glycoproteins whose expression is inhibited in Fos
transformed cells, but not in revertant cell lines that produce comparable
levels of the Fos protein. cDNA libraries enriched for genes whose
expression is altered by Fos transformation will be prepared by subtractive
hybridization between mRNA's expressed in the transformed cells and the
revertants. These libraries will be used to clone additional genes whose
altered expression either negative or positive is specifically associated
with Fos-induced transformation. Once isolated, the cis-acting regulatory
regions that control the transcription of these genes will be identified
and defined. These regulatory sequences will then be used to purify the
transacting factors which interact with these sequences to alter gene
expression. Once purified, the proteins will be sequenced and
oligonucleotide probes developed to molecularly clone and characterize the
corresponding genes. These studies will thus provide insight into the
aberrent mechanisms of gene regulation associated with Fos induced cell
transformation.
StatusFinished
Effective start/end date7/1/906/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $166,585.00

ASJC

  • Medicine(all)

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