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Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin.

Hoi, Charlene S L; Lee, Song Eun; Lu, Shu-Yang; McDermitt, David J; Osorio, Karen M; Piskun, Caroline M; Peters, Rachel M; Paus, Ralf; Tumbar, Tudorita

Molecular and cellular biology. 2010;30(10):2518-36.

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Abstract

Runx1/AML1 is a transcription factor implicated in tissue stem cell regulation and belongs to the small Runx family of cancer genes. In the hair follicle (HF), Runx1 epithelial deletion in morphogenesis impairs normal adult hair homeostasis (cycle) and blocks adult hair follicle stem cells (HFSCs) in quiescence. Here, we show that these effects are overcome later in adulthood. By deleting Runx1 after the end of morphogenesis, we demonstrate its direct role in promoting anagen onset and HFSC proliferation. Runx1 deletion resulted in cyclin-dependent kinase inhibitor Cdkn1a (p21) upregulation. Interfering with Runx1 function in cultured HFSCs impaired their proliferation and normal G(0)/G1 and G(1)/S cell cycle progression. The proliferation defect could be rescued by Runx1 readdition or by p21 deletion. Chemically induced skin tumorigenesis in mice turned on broad Runx1 expression in regions of the skin epithelium, papillomas, and squamous cell carcinomas. In addition, it revealed reduced rates of tumor formation in the absence of Runx1 that were accompanied by decreased epithelial levels of phospho-Stat3. Runx1 protein expression was similar in normal human and mouse hair cycles. We propose that Runx1 may act as a skin oncogene by directly promoting proliferation of the epithelial cells.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
30
Issue:
10
Pagination:
2518-36
Digital Object Identifier:
10.1128/MCB.01308-09
Pubmed Identifier:
20308320
Pii Identifier:
MCB.01308-09
Funder acknowledgement:
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:145533
Created by:
Paus, Ralf
Created:
6th January, 2012, 14:34:56
Last modified by:
Paus, Ralf
Last modified:
6th January, 2012, 14:34:56

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