Patterns of cell signaling pathway activation that characterize mammary development.
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.
Duke Institute for Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Eran R
ER
Andrechek
Seiichi
S
Mori
Rachel E
RE
Rempel
Jeffrey T
JT
Chang
Joseph R
JR
Nevins
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000637:transplantation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007774:Lactation / Q000235:genetics / Q000502:physiology; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
D050684:E2F Transcription Factors