# GROWTH FACTOR INDEPENDENCE IN MAMMARY NEOPLASIA

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1989 · $138,202

## Abstract

The broad objective of this project is to identify specific
alterations in growth control mechanisms that are causally related
to the neoplastic growth potential of rat mammary carcinoma (RMT)
cells.  To accomplish this, experiments have focused on
understanding growth control mechanisms operative for normal rat
mammary epithelial (RME) cells and from that perspective examining
for normal rat mammary epithelial (RME) cells and from that
perspective examining growth control in corresponding tumor derived
cells.  We have found that, whereas RME cells have a finite and
reproducible proliferative lifespan in culture, every primary tumor
examined has cells that are immortal with respect to their
proliferative potential in culture.  Despite this difference, no
all immortal RMT cells express neoplastic potential when
transplanted into syngeneic hosts.  However, immortal RMT cells
that also have become independent of growth factors strictly
required by RME cells for growth in serum-free culture express high
neoplastic potential upon transplantation to syngeneic recipients.
Therefore, this project is aimed at determining the cellular and
molecular basis for the acquisition of growth factor independence
by neoplastic cells and to test directly the hypothesis that growth
factor independence is causally related to neoplastic potential.
The specific aims are:  1) To determine if the loss of specific
growth factor requirements by growth factor independent RMT cells
results from growth factor synthesis by these cells and if so, to
identify and characterize the autocrine factors responsible for
this altered phenotype.  2) To determine if induction of growth
factor independence in normal RME cells or in immortalized growth
factor dependent RMT cells by chemical carcinogen treatment in
vitro results in concomitant acquisition of neoplastic potential
in vivo; and 3) To test the hypothesis that some (or all) growth
factor independent RMT cells became so by mechanism not directly
involving growth factor synthesis, but via activation of proto-
oncogenes that are homologous to growth factor receptors, (e.g. c-
erbB or e.g. c-erbB-2) or that act in growth factor mediated signal
transduction (e.g. c-ras).

## Key facts

- **NIH application ID:** 3179512
- **Project number:** 2R01CA040064-04A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** STEPHEN P. ETHIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $138,202
- **Award type:** 2
- **Project period:** 1985-07-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179512

## Citation

> US National Institutes of Health, RePORTER application 3179512, GROWTH FACTOR INDEPENDENCE IN MAMMARY NEOPLASIA (2R01CA040064-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179512. Licensed CC0.

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