Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

Stein, T., Morris, J.S., Davies, C.R., Weber-Hall, S.J., Duffy, M.A., Heath, V.J., Bell, A.K., Ferrier, R.K., Sandilands, G.P. and Gusterson, B.A. (2004) Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Research, 6(2), R75-R91.

Abstract

INTRODUCTION: Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS: We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanism of controlled involution after withdrawal of the pups at day seven of lactation. Some of the results were confirmed by semi-quantitative reverse transcriptase polymerase chain reaction, Western blotting or immunohistochemistry. RESULTS: We identified 145 genes that were specifically upregulated during the first 4 days of involution; of these, 49 encoded immunoglobulin genes. A further 12 genes, including those encoding the signal transducer and activator of transcription 3 (STAT3), the lipopolysaccharide receptor (CD14) and lipopolysaccharide-binding protein (LBP), were involved in the acute-phase response, demonstrating that the expression of acute-phase response genes can occur in the mammary gland itself and not only in the liver. Expression of LBP and CD14 was upregulated, at both the RNA and protein level, immediately after pup withdrawal; CD14 was strongly expressed in the luminal epithelial cells. Other genes identified suggested neutrophil activation early in involution, followed by macrophage activation late in the process. Immunohistochemistry and histological staining confirmed the infiltration of the involuting mammary tissue with neutrophils, plasma cells, macrophages and eosinophils. CONCLUSION: Oligonucleotide microarrays are a useful tool for identifying genes that are involved in the complex developmental process of mammary gland involution. The genes identified are consistent with an immune cascade, with an early acute-phase response that occurs in the mammary gland itself and resembles a wound healing process.

• Item Type: Articles
• Additional Information: This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
• Keywords: acute-phase response, involution, mammary gland, microarray
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ferrier, Mr Roderick and Stein, Dr Torsten and Gusterson, Professor Barry and Bell, Miss Alexandra and Morris, Professor Joanna
• Authors: Stein, T., Morris, J.S., Davies, C.R., Weber-Hall, S.J., Duffy, M.A., Heath, V.J., Bell, A.K., Ferrier, R.K., Sandilands, G.P., and Gusterson, B.A.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Breast Cancer Research
• Publisher: Biomed Central
• ISSN: 1465-5411
• ISSN (Online): 1465-542X
• Copyright Holders: © 2004 Stein et al., licensee BioMed Central Ltd
• First Published: First published in Breast Cancer Research 6(2)
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher