# ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 1987 · $93,932

## Abstract

We have observed that normal mouse mammary gland, not unlike certain human
and rodent mammary neoplasias, can also become refractory to
hormone-dependent growth regulation; however, in contrast to mammary
tumors, in normal mammary gland this refractoriness is fully reversible.
Estrogen and progesterone, two major growth regulatory hormones in mammary
gland, are believed to produce their biologic effects via
hormone-receptor-mediated mechanisms.  Recent studies of estrogen receptor
ontogeny in the uterus have shown that receptors appear in the stroma
before they appear in the epithelium.  However, hormone exposure of the
tissue at a time when receptors are present only in the stroma results in
cell proliferation in the epithelium.  It has been hypothesized that
hormonally-induced growth factors in stromal cells are responsible for the
growth of the epithelium.  The specific aim of the proposed research is to
determine if regulation of epithelial cell proliferation by estrogen and/or
progesterone in mammary gland occurs directly in response to these hormones
or whether it is mediated indirectly by the response of the stromal cells.
The first step will be to determine the distribution of estrogen (ER) and
progesterone receptors (PgR) in the various epithelial and stromal cell
types that make up the range of mammary gland structures.  Mammary glands
at different developmental stages with differing responses to estrogen and
progesterone will be examined:  (1) early postnatal gland will be
investigated to determine the ontogeny of ER and PgR in epithelial and
stromal cells in relation to the ontogeny of cell proliferative responses
to estrogen and progesterone; (2) adult virgin gland will be studied as a
highly responsive state to the cell proliferative effects of both estrogen
and progesterone; and (3) postpartum gland will be studied for potential
changes in cellular distribution of ER and/or PgR that could account for
the refractoriness to growth regulation that is observed during lactation.
Cellular localization of ER and PgR will be determined histologically by
the technique of steroid autoradiography.  For all of the developmental
stages in vivo cell proliferation in response to treatment with estrogen or
progesterone will be quantitated, in parallel, by DNA historadiography.
Such studies will provide important insights into the roles of stromal and
epithelial cells in mediating and/or modifying growth regulation by
estrogen and/or progesterone, the basis for refractoriness to growth
regulation in mammary cancer, and the therapeutic reversal of hormone
independence in human mammary cancer.  (D)

## Key facts

- **NIH application ID:** 3179635
- **Project number:** 5R01CA040104-03
- **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:** 1987
- **Award amount:** $93,932
- **Award type:** 5
- **Project period:** 1985-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179635

## Citation

> US National Institutes of Health, RePORTER application 3179635, ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION (5R01CA040104-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179635. Licensed CC0.

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