Runx1 Directly Promotes Proliferation of Hair Follicle Stem Cells and Epithelial Tumor Formation in Mouse Skin
| Autor: | Shu Y. Lu, Rachel M. Peters, Caroline M. Piskun, Song Eun Lee, Ralf Paus, Tudorita Tumbar, Karen M. Osorio, Charlene S. L. Hoi, David J. McDermitt |
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| Rok vydání: | 2010 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Keratinocytes Male Recombinant Fusion Proteins Cell Morphogenesis Biology medicine.disease_cause Mice hemic and lymphatic diseases medicine Animals Humans Cell Lineage Neoplasms Glandular and Epithelial Molecular Biology Cells Cultured Cell Proliferation Skin Mice Knockout integumentary system Oncogene Cell growth Stem Cells Cell Cycle Articles Cell Biology Hair follicle Epithelium Cell biology Mice Inbred C57BL Phenotype medicine.anatomical_structure Core Binding Factor Alpha 2 Subunit embryonic structures Cancer research Female Stem cell Carcinogenesis Hair Follicle Biomarkers |
| Zdroj: | Molecular and Cellular Biology. 30:2518-2536 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.01308-09 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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