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Publication : Defining the origins of Ras/p53-mediated squamous cell carcinoma.

First Author  White AC Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  18 Pages  7425-30
PubMed ID  21502519 Mgi Jnum  J:172216
Mgi Id  MGI:5005007 Doi  10.1073/pnas.1012670108
Citation  White AC, et al. (2011) Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A 108(18):7425-30
abstractText  The precise identity of cancer cells of origin and the molecular events of tumor initiation in epidermal squamous cell carcinoma (SCC) are unknown. Here we show that malignancy potential is related to the developmental capacity of the initiating cancer cell in a genetically defined, intact, and inducible in vivo model. Specifically, these data demonstrate that SCCs can originate from inside the hair follicle stem cell (SC) niche or from immediate progenitors, whereas more developmentally restricted progeny, the transit amplifying (TA) cells, are unable to generate even benign tumors in the same genetic context. Using a temporal model of tumorigenesis in situ, we highlight the phenotypes of cancer progression from the hair follicle SC niche, including hyperplasia, epithelial to mesenchymal transition, and SCC formation. Furthermore, we provide insights into the inability of hair follicle TA cells to respond to tumorigenic stimuli.
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