2024-03-28T12:32:42Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/630482016-02-17T10:38:34Zcom_10261_112com_10261_1col_10261_365
Spontaneous Squamous Cell Carcinoma Induced by the Somatic Inactivation of Retinoblastoma and Trp53 Tumor Suppressors
Lara, M. Fernanda
Segrelles, Carmen
Ruiz Macías, Sergio
Squamous cell carcinomas (SCC) represent the most aggressive type of nonmelanoma skin cancer. Although little is known about the causal alterations of SCCs, in organ-transplanted patients the E7 and E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved. Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that p53 is the predominant tumor suppressor acting in mouse epidermis. Although the simultaneous inactivation of pRb and p53 does not aggravate the phenotype observed in Rb-deficient epidermis in terms of proliferation and/or differentiation, spontaneous SCC development is severely accelerated in doubly deficient mice. The tumors are aggressive and undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the epidermal growth factor receptor/Akt pathway, resulting in increased proliferation in normal and dysplastic hair follicles and augmented tumor angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer. ©2008 American Association for Cancer Research.
Oncocycle (CAM), ISCIII-RETIC RD06/0020 (MSC), SAF2005-00033 (MCYT), and Oncology Program from La Caixa Foundation (J.M. Paramio). M. Moral is a recipient of a FIS-BEFI Predoctoral Fellowship from MSC (BF03-00201).
Peer Reviewed
2012-12-17T11:51:32Z
2012-12-17T11:51:32Z
2008
2012-12-17T11:51:32Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1158/0008-5472.CAN-07-3049
issn: 0008-5472
e-issn: 1538-7445
Cancer Research 68(3): 683-692 (2008)
http://hdl.handle.net/10261/63048
10.1158/0008-5472.CAN-07-3049
en
none
American Association for Cancer Research