REGULATION OF C-FMS PROTO-ONCOGENE IN EPITHELIAL CANCERS

Project: Research project

Project Details

Description

The c-fms proto-oncogene encodes the receptor for a hematopoietic growth
factor, CSF-1. There has been increasing recognition of c-fms and its
ligand CSF-1 in malignancies of non-hematopoietic origin, such as breast
and ovarian cancers. We initially studied breast carcinoma cell lines in
which dexamethasone (dex) treatment results in marked overexpression of
both c-fms steady-state transcript and protein levels. Our results of
c-fms mRNA stability and transcription rate are compatible with
regulation of c-fms expression by dex at the post-transcriptional level.
Induction of c-fms is dependent on transcription of a glucocorticoid
responsive factor. Our results indicate that this factor may be a
regulatory protein which stabilizes c-fms transcripts, leading to c-fms
overexpression. In this application, we focus on first elucidating the
c-fms transcript sequence responsible for mRNA stability upon exposure to
dex, and then characterizing the RNA-protein complex and binding site
important to stabilization and overexpression of the c-fms transcript.
We propose to use methodologies which have been employed to define other
sequences important to glucocorticoid inducible mRNA stability and those
used to characterize other protein-RNA regulatory complexes, such as the
AUUUA-specific mRNA binding protein. A greater understanding of the
mechanism underlying regulation of the c-fms proto-oncogene is important,
as both c-fms and its ligand CSF-1 appear to contribute to the invasive
phenotype and/or poor prognosis associated with carcinomas of breast,
ovarian, endometrial, and placental origin. Elucidation of such a
sequence, which may represent a consensus sequence through which c-fms
expression is regulated, would lead to development of therapeutic
strategies which interfere with protein binding to this site, resulting
in downregulation of c-fms expression.
StatusFinished
Effective start/end date4/1/933/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $81,810.00

ASJC

  • Medicine(all)

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