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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 18
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pubmed:dateCreated |
2004-8-18
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pubmed:abstractText |
The forkhead transcription factor FOXN1 is required for normal cutaneous and thymic epithelial development. Mutations in FOXN1 give rise to the nude phenotype in mice, rats and man. However, the genes that are regulated by FOXN1 are unknown. To investigate FOXN1 function we expressed an inducible form of the protein, FOXN1ER, that is activated by 4-hydroxytamoxifen in primary human epidermal keratinocytes. Transient activation of FOXN1 decreased the proportion of keratinocytes that formed actively growing clones attributable to stem cell founders and increased the number of abortive clones, without inducing apoptosis. Within 24 hours the majority of cells had initiated terminal differentiation, as assessed by involucrin expression. We performed a cDNA microarray experiment to analyse changes in the transcription of approximately 6,000 genes. Following FOXN1 activation we detected increases of two fold or greater in the RNA levels of over 30 genes. Genes promoting growth arrest, survival and differentiation featured prominently and markers of early events in keratinocyte differentiation were also detected. Since one of the induced genes was Akt we investigated whether Akt played a role in terminal differentiation. Activation of PI 3-kinase but not Akt was necessary for FOXN1-induced differentiation. In reconstituted epidermis FOXN1 promoted early stages of terminal differentiation whereas Akt activation was sufficient to induce late stages, including formation of the cornified layers. These results establish a role for FOXN1 in initiation of terminal differentiation and implicate Akt in subsequent events.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Whn protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9533
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4157-68
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15316080-Cell Differentiation,
pubmed-meshheading:15316080-Cell Proliferation,
pubmed-meshheading:15316080-Cell Survival,
pubmed-meshheading:15316080-Cells, Cultured,
pubmed-meshheading:15316080-Clone Cells,
pubmed-meshheading:15316080-DNA-Binding Proteins,
pubmed-meshheading:15316080-Epidermis,
pubmed-meshheading:15316080-Forkhead Transcription Factors,
pubmed-meshheading:15316080-Gene Expression Profiling,
pubmed-meshheading:15316080-Gene Expression Regulation,
pubmed-meshheading:15316080-Humans,
pubmed-meshheading:15316080-Keratinocytes,
pubmed-meshheading:15316080-Male,
pubmed-meshheading:15316080-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:15316080-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15316080-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15316080-Proto-Oncogene Proteins,
pubmed-meshheading:15316080-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15316080-RNA, Messenger,
pubmed-meshheading:15316080-Stem Cells,
pubmed-meshheading:15316080-Tamoxifen,
pubmed-meshheading:15316080-Transcription Factors,
pubmed-meshheading:15316080-Transcriptional Activation,
pubmed-meshheading:15316080-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt.
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pubmed:affiliation |
Keratinocyte Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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