# REGULATION OF C-FMS PROTO-ONCOGENE IN EPITHELIAL CANCERS

> **NIH NIH K08** · YALE UNIVERSITY · 1994 · $81,810

## Abstract

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.

## Key facts

- **NIH application ID:** 2194538
- **Project number:** 5K08HD001013-02
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** SETSUKO KUKI CHAMBERS
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $81,810
- **Award type:** 5
- **Project period:** 1993-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194538

## Citation

> US National Institutes of Health, RePORTER application 2194538, REGULATION OF C-FMS PROTO-ONCOGENE IN EPITHELIAL CANCERS (5K08HD001013-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194538. Licensed CC0.

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