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Breast Cancer Research
Published in: Breast Cancer Research 2/2004

Open Access 01-04-2004 | Research article

Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression

Authors: Richard WE Clarkson, Matthew T Wayland, Jennifer Lee, Tom Freeman, Christine J Watson

Published in: Breast Cancer Research | Issue 2/2004

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Abstract

Introduction

In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution.

Method

Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function.

Results

The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor–Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity.

Conclusion

We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment.
Appendix
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Metadata
Title
Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression
Authors
Richard WE Clarkson
Matthew T Wayland
Jennifer Lee
Tom Freeman
Christine J Watson
Publication date
01-04-2004
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2004
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr754

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