# SOMATOMEDIN ACTIONS IN NORMAL AND TRANSFORMED CELLS

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1990 · $160,277

## Abstract

The somatomedins are polypeptide hormones which stimulate the
replication of many normal and transformed cell types.  Two
somatomedins have been identified in humans:  insulin-like growth
factors I and II (IGF-I and IGF-II).  The objectives of the studies
described in this proposal are to characterize the mechanism by
which these hormones elicit their mitogenic effect and to asses
their role in stimulating human tumor growth in vivo.

Both of the IGFs stimulate replication by binding to the same cell
surface receptor, the type I IGF receptor, but the mechanism by
which this binding initiates the replicative response is not
understood.  Other growth factors stimulate the internalization of
their receptors and it has been postulated that the internalized
receptors catalyze the tyrosine-specific phosphorylation of key
intracellular proteins and, by binding to the nucleus, regulate the
expression of specific genes.  The first aim of these studies is
to investigate the metabolism of the type I IGF receptor in human
cells:  the internalization, degradation and recycling of this
receptor will be examined, the tyrosine-kinase activity of the
internalized receptor will be characterized, and nuclear
translocation of the receptor will be investigated.  The second aim
of these studies is to identify the intracellular substrates of the
internalized receptor tyrosine-kinase and to characterize the
effects of the IGFs on the transcription of specific genes and the
synthesis of selective proteins.

A number of alterations in the IGF-receptor pathway could result
in a loss of normal growth control and contribute to the abnormal
growth of transformed cells.  The third aim of these studies is to
identify specific alterations in the IGF-receptor pathway occurring
in transformed human cells in vitro and to determine if these
alterations are characteristic of particular tumor cell types.  The
final aim is to determine if these alterations are important in
stimulating tumor growth in vivo.  To study this transformed human
cell lines will be grown as tumors in nude mice and the effects of
altering tissue IGF levels and of inhibiting IGF receptor function
on tumor growth will be investigated.

The information gained from these studies should lead to a better
understanding of the mechanisms by which the IGFs regulate cell
division and of how this regulation is modified in cancer cells.
Such information may be valuable for designing new approaches for
diagnosing and treating specific human cancers.

## Key facts

- **NIH application ID:** 3177542
- **Project number:** 5R01CA038981-07
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** RICHARD W FURLANETTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $160,277
- **Award type:** 5
- **Project period:** 1984-12-01 → 1993-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177542

## Citation

> US National Institutes of Health, RePORTER application 3177542, SOMATOMEDIN ACTIONS IN NORMAL AND TRANSFORMED CELLS (5R01CA038981-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177542. Licensed CC0.

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