Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse stratified epithelial spontaneous SCC induced by the somatic inactivation of Rb1 and Trp53 tumor suppressors


ABSTRACT: The squamous cell carcinomas represent the aggressive type of non melanoma skin cancer, the most frequent malignancy among human population. We have studied here the possible relationship between these two pathways in skin using epidermal-specific mutant mice. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that, contrary to pRb, p53 is the predominant tumor suppressor acting in mouse epidermis. The simultaneous inactivation of pRb and p53 does not aggravate the epidermal phenotype observed in Rb-deficient mice in terms of proliferation and/or differentiation. However, in doubly deficient mice spontaneous skin tumor development is severely accelerated. The tumors are aggressive, undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the EGFR/Akt pathway, resulting in increased 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. Experiment Overall Design: Pools from RNA whole skin extracts from 3 animals of same genotype were done and analyzed, per duplicate, in mouse microarrays. Comparison was performed between the 4 different genotypes.

ORGANISM(S): Mus musculus

SUBMITTER: Ramón García-Escudero 

PROVIDER: E-GEOD-9144 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors.

Martínez-Cruz Ana Belén AB   Santos Mirentxu M   Lara M Fernanda MF   Segrelles Carmen C   Ruiz Sergio S   Moral Marta M   Lorz Corina C   García-Escudero Ramón R   Paramio Jesús M JM  

Cancer research 20080201 3


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 spo  ...[more]

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