Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy.

Molecular Cancer
Ramón García-EscuderoJesús M Paramio

Abstract

The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in addit...Continue Reading

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Citations

Dec 6, 2012·Journal of Drug Delivery·Duncan Ayers, Alessandro Nasti
Nov 13, 2012·Scientific Reports·Clotilde CostaJesús M Paramio
Jun 6, 2012·Scientific Reports·Olga BornacheaJesús M Paramio
Sep 13, 2011·Acta Biochimica Et Biophysica Sinica·Luqing ZhaoYa Cao
Sep 5, 2013·Physiological Genomics·Yuwen LiSamir S El-Dahr
Apr 3, 2020·The Journal of Investigative Dermatology·Sukhinder K CheemaEnrique C Torchia

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Datasets Mentioned

BETA
GSE11990
GSE19616

Methods Mentioned

BETA
transgenic
acetylation
chip

Software Mentioned

Ttest
Multiexperiment Viewer
MeV
DAVID Functional Annotation web tool
SPSS
Significant Analysis of Microarrays ( SAM )
Discriminant Analysis Module ( DAM )
Gene Set Enrichment Analysis ( GSEA )
SAM
GSEA

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