# LIPID MODULAT OF MAMMARY PROLIFER & DIFFERENTIATION

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1992 · $136,194

## Abstract

The objective of the proposed studies is to investigate the effect of lipid
on the proliferation and differentiation of normal rat mammary epithelial
cells (rmec), with the long-term goal of understanding the mechanism by
which diets high in polyunsaturated fat stimulate mammary tumorigenesis. It
is proposed that alterations of membrane phospholipid composition modulate
the receptor transducing mechanism for hormones and growth factors, thus
affecting cell proliferation and differentiation. Specific emphasis will be
placed on protein kinase C, since this enzyme, which plays a major role in
intracellular signal transduction, requires lipid for its activity. These
studies will be carried out using a primary culture model system recently
developed in our laboratory in which rat mammary epithelial cells obtained
from immature virgin rats are grown within a reconstituted basement
membrane matrix in a serum-free defined medium. This model allows for both
extensive proliferation of the mammary epithelial cells (15-30 fold within
14-21 days) as well as functional and morphological differentiation
equivalent to that of the lactating mammary gland. AIM 1. To carry out a
comprehensive study of the effects of specific hormones and growth factors
on morphological and functional differentiation of normal rat mammary
epithelial cells in primary culture, with the goal of completing
characterization of this unique model system. These studies will serve as
the foundation upon which the effects of lipid as well as other protein
kinase C modulators can be investigated. AIM 2. To continue studies on the
effects of lipid on proliferation as well as morphological and functional
differentiation of normal rat mammary epithelial cells. These studies will
focus on the hormonal and growth factor conditions under which fatty acids
and other lipids modulate specific mammary epithelial cell functions, with
the goal of identifying those growth factors whose activity can be
regulated by changes in membrane lipid composition and/or by the lipid in
the incubation medium, and the mechanism by which this action is mediated.
AIM 3. To determine the role of specific protein kinase C isoenzymes in the
proliferation and differentiation of normal rat mammary epithelial cells.
In these studies, protein kinase C will be monitored during development of
both morphological and functional differentiation, as well as in response
to specific combinations of hormones and growth factors known to favor
either the differentiation or proliferation of the mammary cells.
Considerable emphasis will be placed on defining the effect of individual
hormones and growth factors on the activity and isoenzyme composition of
protein kinase C and the effect of protein kinase C inhibitors and
activators on proliferation and differentiation. AIM 4. To determine if
changes in membrane phospholipid composition affect receptor transducing
mechanisms, with specific emphasis on protein kinase C. In this aim, the
effect ...

## Key facts

- **NIH application ID:** 3171213
- **Project number:** 5R01CA033240-10
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** MARGOT M IP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $136,194
- **Award type:** 5
- **Project period:** 1982-09-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171213

## Citation

> US National Institutes of Health, RePORTER application 3171213, LIPID MODULAT OF MAMMARY PROLIFER & DIFFERENTIATION (5R01CA033240-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171213. Licensed CC0.

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