# STROMA AND MAMMARY GLAND CELL PROLIFERATION

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 1993 · $174,689

## Abstract

In the previous grant period we have delineated the ontogeny of
responsiveness of the normal mouse mammary gland to growth regulation
by estrogen (E) and progesterone (P) in relation to the ontogeny of
estrogen (ER) and progesterone receptor (PR) cellular distribution.
We discovered that there is a sequential acquisition of responsiveness,
such that E-inducible proliferation is observed first at 3 weeks of
age, whereas E-inducible PR and P-inducible proliferation are detected
later, at 7 weeks.  However, ER are detected as early as 3 days of age
in both epithelial and stromal cells and the lack of a proliferative
response at this age indicates that non-steroidal growth factors are
likely to be biologically relevant mitogens and regulators of mammary
gland growth and function in vivo. In this regard, we find that
epidermal growth factor (EGF) can mediate the proliferative effective
of E at early ages in vivo.  In addition, in vitro in organ culture,
treatment with EGF+E causes the precocious acquisition of E-inducible
PR.  Furthermore, our studies demonstrate that adult mammary stroma
also can cause the precocious acquisition of E-inducible PR in immature
3 week old epithelium.  Thus the insights obtained by us in the
previous grant period put us in a strong position to now determine the
molecular mechanisms mediating epithelial-stromal cell interactions and
the acquisition of hormonal responsiveness in the normal mouse gland.
We hypothesize that 1) changes in specific growth factor (EGF,
TGF-alpha, bFGF, IGF-I, II) or growth inhibitor (TGF-beta) levels in
epithelial and/or stromal cells and/or 2) changes in specific
extracellular matrix (ECM) components (collagen I, IV, laminin,
fibronectin, tenascin) are correlated with the acquisition of
responsiveness to E and P in vivo.  Each of these growth
factors/inhibitors and ECM components have been implicated to affect
mammary gland growth and function.  Our goal will be to then test the
biological relevance of these changes using in vivo and in vitro
approaches.  Detailed analysis of the molecular mechanisms underlying
the epithelial-stromal cell interactions which result in the transition
from a hormonally non-responsive to a responsive state may lead to new
therapeutic strategies for the treatment of breast cancer.

## Key facts

- **NIH application ID:** 3179632
- **Project number:** 2R01CA040104-09
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **SAM.gov UEI:** R28EKN92ZTZ9
- **Principal Investigator:** SANDRA Z HASLAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $174,689
- **Award type:** 2
- **Project period:** 1985-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179632

## Citation

> US National Institutes of Health, RePORTER application 3179632, STROMA AND MAMMARY GLAND CELL PROLIFERATION (2R01CA040104-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179632. Licensed CC0.

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