# LIPID TURNOVER & GROWTH OF NORMAL & TUMOR MAMMARY CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 1992 · $209,148

## Abstract

The long-term objective of this application is to elucidate the
mechanism of lipid involvement in growth regulation of normal
and tumor mammary epithelial cells (MEC).  Isolated normal
MEC, embedded in collagen gel, proliferate and differentiate in
response to growth factors, mammogenic hormones and 18:2, (n-
6).  Analyzing the effects of 18:2 on normal MEC proliferation, it
was found that the eicosanoids, PGE2 and HETEs, can synergize
with each other in sustaining proliferation of MEC in the presence
of EGF in basal medium with insulin.  Other agents like TPA,
lithium, cAMP and di(18:2)-phosphatidic acid can support growth
of MEC in basal medium in the absence of growth factors or
mammogenic hormones.  These observations indicate the
involvement of a lipid-responsive pathway in MEC proliferation.
The components of this pathway may include metabolites of
phospholipid turnover, eicosanoids, protein kinase A and protein
kinase-C.  Unlike normal MEC, tumor cells are heterogeneous
and, consequently, vary in their proliferative response to 18:2.  It
was observed that, while some tumor cells are dependent on 18:2
for maximum growth, others are not.  The reports concerning
inhibition of mammary tumor growth in rodents by feeding (n-3)
PUFA may be explained as direct intervention of 18:2 and 20:4
metabolism by dietary (n-3) PUFA.  In order to uncover the
details of a lipid-responsive pathway which may explain the role
of (n-6) and (n-3) PUFA, the following studies are being proposed
to determine:  (a) whether all hormonal and nonhormonal growth
promoters of MEC require metabolites of (n-6) PUFA for
sustained cell proliferation, (b) whether products of phospholipid
turnover and Pl-cycle intermediates are involved in the
generation of proliferative signals, (c) whether any difference in
the production of and responsiveness to eicosanoids, cAMP and
cGMP, characterize the difference between the 18:2-dependent
and -independent mammary tumors, (d) whether (n-3) PUFA
regulate proliferation of normal and neoplastic MEC by inhibiting
eicosanoid production from 20:4 (n-6) and finally, (e) whether
kinase A and kinase-C are associated with the putative lipid-
responsive pathway for cell proliferation.  A major part of the
work will be carried out in serum-free culture system using
normal and neoplastic mouse MEC.  The effects on growth will be
examined in the presence of absence of lipid analogues or enzyme
inhibitors.  Lipid turnover will be studied by exposing cells,
prelabelled with precursors, to agonists.  Lipids (including
eicosanoids) and cyclic nucleotides will be analyzed by
chromatography and/or RIA.  cell-free protein kinase activities,
phosphorylation of 80 kDa protein and binding of labeled PDBu, in
response to agonists, will be determined.  Working through this
project, we hope to be able to understand how lipids regulate
growth of normal and tumor mammary tissues which might
provide ways for future preventive and therapeutic measures.

## Key facts

- **NIH application ID:** 3179739
- **Project number:** 5R01CA040160-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **SAM.gov UEI:** GS3YEVSS12N6
- **Principal Investigator:** Satyabrata Nandi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $209,148
- **Award type:** 5
- **Project period:** 1985-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179739

## Citation

> US National Institutes of Health, RePORTER application 3179739, LIPID TURNOVER & GROWTH OF NORMAL & TUMOR MAMMARY CELLS (5R01CA040160-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179739. Licensed CC0.

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