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First published online 11 June 2008
doi: 10.1242/dev.019018

Development 135, 2403-2413 (2008)
Published by The Company of Biologists 2008
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Patterns of cell signaling pathway activation that characterize mammary development

Eran R. Andrechek, Seiichi Mori, Rachel E. Rempel, Jeffrey T. Chang and Joseph R. Nevins*

Duke Institute for Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

* Author for correspondence (e-mail: nevin001{at}mc.duke.edu)

Accepted 12 May 2008

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.

Key words: E2F transcription factor, Mammary gland, Microarray, Mouse






© The Company of Biologists Ltd 2008