Abstract 491: Defining the origins of ras/p53 mediated squamous cell carcinoma

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 hair follicle stem cells (SCs) serve as cancer cells of origin when oncogenic Kras is expressed and p53 is ablated, whereas their more developmentally restricted progeny, the transit amplifying (TA) cells, are unable to generate even benign tumors in the same genetic context. Employing a temporal model of tumorigenesis in situ, we highlight the phenotypes of cancer progression from hair follicle SCs including hyperplasia, dysplasia, epithelial to mesenchymal transition, and SCC formation. Furthermore, we provide insights into the inability of hair follicle TA cells to respond to tumorigenic stimuli. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 491. doi:10.1158/1538-7445.AM2011-491