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PMID: 18550711 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Patterns of cell signaling pathway activation that characterize mammary development.

Development (Cambridge, England) ·Vol. 135 ·No. 14 ·2008-08-00 ·Pages 2403-13

Andrechek ER, Mori S, Rempel RE, Chang JT, Nevins JR

Abstract

Previous work has detailed the histological and biochemical changes associated with mammary development and remodeling. We have now made use of gene expression profiling, and in particular of the previously described signatures of cell signaling pathway activation, to explore the events associated with mammary gland development. We find that there is elevated E2F-specific pathway activity prior to lactation and relatively low levels of other important signaling pathways, such as RAS, MYC and SRC. Upon lactation and continuing into the involution phase, these patterns reverse with a dramatic increase in RAS, SRC and MYC pathway activity and a decline in E2F activity. At the end of involution, these patterns return to that of the adult non-lactating mammary gland. The importance of the changes in E2F pathway activity, particularly during the proliferative phase of mammary development, was confirmed through the analysis of mice deficient for various E2F proteins. Taken together, these results reveal a complex pattern of pathway activity in relation to the various phases of mammary gland development.

MeSH Terms
Animals Apoptosis Cells, Cultured E2F Transcription Factors/genetics,metabolism Epithelial Cells/transplantation Gene Expression Profiling Gene Expression Regulation, Developmental Heterozygote Immunohistochemistry In Situ Nick-End Labeling Lactation/genetics,physiology Mammary Glands, Animal/growth & development,metabolism Mice Mice, Knockout Mice, Nude Models, Biological Mutation Oligonucleotide Array Sequence Analysis Signal Transduction/genetics Time Factors
Chemicals
E2F Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Andrechek Eran R
Duke Institute for Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Mori Seiichi
Rempel Rachel E
Chang Jeffrey T
Nevins Joseph R
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
DOI
10.1242/dev.019018
Published
2008-08-00
Epub
2008-00-11
Pages
2403-13
Language
English
Region
England
NLM ID
8701744
PMCID
PMC3615553
Subset
IM
Grants
NCI NIH HHS · R01 CA106520 · United States
NLM NIH HHS · K99 LM009837 · United States
NCI NIH HHS · 5-R01-CA106520-04 · United States
NLM NIH HHS · R00 LM009837 · United States
NCI NIH HHS · 5 U24 CA112952-04 · United States
NCI NIH HHS · U54 CA112952 · United States
External Links
PubMed source DOI: 10.1242/dev.019018 PMC Full Text View journal details
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