# Integrin Regulation of Mammary Gland Development

> **NIH NIH F31** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $32,882

## Abstract

PROJECT SUMMARY
The mammary epithelium is composed of diverse cell populations that are responsible for regulating key
processes in mammary gland development, especially lactation. Alveolar progenitor (AP) cells are partially
differentiated stem cells that produce alveolar/milk-producing cells and these cells have recently been implicated
as cells of origin in breast cancer. Through analysis of published single cell RNA-seq data, integrin β4, a protein
known to function primarily in basal mammary epithelial cells to maintain structural integrity of the gland, was
found to be expressed in the AP population. This unexpected result suggests that β4 plays a novel role in the
AP population and may regulate dynamic processes within the developing mammary gland. This goal of this
proposal is to understand the functional role of β4 in the AP cells of the nulliparous and lactating mammary gland
and elucidate the mechanism by which β4 regulates this population. Preliminary studies have revealed that β4
expression is necessary to promote progenitor potential of the AP cells and identified LacdiNAc, a novel
glycosylation modification, on β4 that we hypothesize is essential for its localization in lipid rafts that promotes
its function in the AP population. Using an AP cell culture model as well as a Cre-lox mouse model to conditionally
knock out β4 from the AP population, the function of β4 in the AP population will be assessed in vitro and in the
virgin and lactating mammary gland. Also, glycomics analyses and biochemical approaches will identify novel
glycans on β4 and help in understanding how LacdiNAc affects function of β4 in the AP population. This
approach will further our understanding of the novel role of β4 in the AP population and a new mechanism
involving LacdiNAc-β4 localization to lipid rafts to regulate alveolar differentiation. These studies have to
potential to define novel mechanisms that regulate the AP population during normal mammary gland
development as well as breast cancer progression.

## Key facts

- **NIH application ID:** 9910322
- **Project number:** 1F31CA239509-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Melanie Rose Walker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,882
- **Award type:** 1
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910322

## Citation

> US National Institutes of Health, RePORTER application 9910322, Integrin Regulation of Mammary Gland Development (1F31CA239509-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9910322. Licensed CC0.

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