# REGULATION OF GROWTH FACTORS AND MAMMALIAN EMBRYOGENESIS

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1994 · $163,796

## Abstract

There is compelling evidence that growth factors regulate both cell
proliferation and differentiation, but little is known about the
mechanisms that regulate growth factor production.  The fibroblast growth
factor k-FGF is one of the first growth factors to be produced during
mammalian development and it is produced by a wide range of tumors.
Recently, embryonal carcinoma (EC) cells have been used to study the
expression and regulation of the k-FGF oncogene.  EC cells, which serve
as an excellent model system for studying early development, have been
shown to produce k-FGF; whereas their differentiated cells do not.
Efforts to understand how k-FGF expression is regulated indicate that
differentiation represses transcription of this gene.  This conclusion is
supported by nuclear run-off studies and by the differential expression
of promoter/reporter gene constructs in EC cells and their differentiated
cells.  Based on the most recent studies in the PI's laboratory, it is
hypothesized that expression of the k-FGF gene in EC cells and their
differentiated cells is controlled by at least three cis-regulatory
elements: an essential enhancer in the third exon of the gene, a positive
cis-regulatory element and a negative cis-regulatory element located
upstream of the transcription start site.  To test this hypothesis and to
determine how expression of this gene is regulated, four Specific Aims
are proposed: 1) Identify and map precisely the location of
cis-regulatory elements that control expression of the k-FGF gene in
mouse EC cells and their differentiated cells. 2) Examine the binding of
nuclear proteins to the cis-regulatory elements that control expression
of the k-FGF gene. 3) Identify the transcription factors that regulate
expression of this gene. 4) Determine how differentiation of EC cells
regulates expression of the transcription factors that regulate
expression of the k-FGF gene.  The work proposed in this application will
address a critical gap in our current knowledge, namely, our limited
understanding of the mechanisms by which growth factor production is
regulated.  Equally important, this work will help advance our
understanding of how differentiation regulates the expression of
transcription factors.

## Key facts

- **NIH application ID:** 2197878
- **Project number:** 5R01HD019837-08
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **SAM.gov UEI:** G15AG3BLLMH4
- **Principal Investigator:** A. ANGIE RIZZINO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $163,796
- **Award type:** 5
- **Project period:** 1985-08-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197878

## Citation

> US National Institutes of Health, RePORTER application 2197878, REGULATION OF GROWTH FACTORS AND MAMMALIAN EMBRYOGENESIS (5R01HD019837-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197878. Licensed CC0.

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