# CELL AGING--GROWTH FACTOR CONTROL OF EARLY RESPONSE GENE

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1991 · $122,032

## Abstract

As normal human cells approach the end of their proliferative lifespan
they fail to respond to a variety of growth factors by replicating their
DNA.  We have examined growth factor responses extensively in WI-38 cells
and have found that they do not result from the loss of necessary growth
factor receptors or recognizable changes in ligand-receptor interactions.
In fact, many of the normal mitogen stimulated cell cycle dependent events
and activities are induced in senescent cells just as they are in young
cells which do respond by entering the S phase.  This has led to the
speculation that senescent cells become blocked in late G1 near the
beginning of the S phase.

Recently we and others (Campisi and co-workers personal communication)
have observed that the mRNA for the protooncogene c-fos appears to be
undetectable in mitogen stimulated senescent cells.  The expression of c-
fos is a very early event following mitogen stimulation, reaching maximum
levels after approximately 0.5 hr in young cells.  We have subsequently
observed that c-fos is actually expressed in senescent WI-38 cells
following either serum or epidermal growth factor stimulation (EGF) but it
is only detectable if protein synthesis is simultaneously inhibited with
cycloheximide.  This is consistent with the disproportionately rapid
degradation of this mRNA in senescent cells.  We intend to study the
regulation of c-fos expression and that of two other early response genes,
c-jun and the serum response factor (SRF) in young and senescent WI-38
cells.  We will examine transcription, protein synthesis and
posttranslational modification by phosphorylation.  We will also directly
test whether c-fos of c-jun can increase the proliferative life span of
WI-38 cells by transforming young cells with plasmids containing these
normal genes under the control of the metallothionein promotor.

## Key facts

- **NIH application ID:** 3121696
- **Project number:** 5R01AG009778-02
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** PAUL D PHILLIPS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $122,032
- **Award type:** 5
- **Project period:** 1990-08-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121696

## Citation

> US National Institutes of Health, RePORTER application 3121696, CELL AGING--GROWTH FACTOR CONTROL OF EARLY RESPONSE GENE (5R01AG009778-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3121696. Licensed CC0.

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