INVESTIGADORES
ABBA Martin Carlos
artículos
Título:
Identification of modulated genes by three classes of chemopreventive agents at pre-neoplastic stages in a p53-null mouse mammary tumor model.
Autor/es:
ABBA MC; MEDINA D; LEVI C; KITTRELL F; HILL J; HILSENBECK S; BROWN PH; ALDAZ CM
Revista:
Cancer Prevention Research
Editorial:
AACR
Referencias:
Año: 2009 vol. 2 p. 175 - 184
ISSN:
1940-6207
Resumen:
Genetically engineered mouse cancer models are among the most useful tools for testingthe in vivo effectiveness of the various chemopreventive approaches. The p53-null mousemodel of mammary carcinogenesis was previously characterized by us at the cellular, molecular,and pathologic levels. In a companion article, Medina et al. analyzed the efficacy ofbexarotene, gefitinib, and celecoxib as chemopreventive agents in the same model. Here wereport the global gene expression effects on mammary epithelium of such compounds, analyzingthe data in light of their effectiveness as chemopreventive agents. SAGE was used toprofile the transcriptome of p53-null mammary epithelium obtained from mice treated witheach compound versus controls. This information was also compared with SAGE data fromp53-null mouse mammary tumors. Gene expression changes induced by the chemopreventivetreatments revealed a common core of 87 affected genes across treatments (P < 0.05).The effective compounds, bexarotene and gefitinib, may exert their chemopreventive activity,at least in part, by affecting a set of 34 genes related to specific cellular pathways. Thegene expression signature revealed various genes previously described to be associatedwith breast cancer, such as the activator protein-1 complex member Fos-like antigen 2(Fosl2), early growth response 1 (Egr1), gelsolin (Gsn), and tumor protein translationally controlled 1 (Tpt1), among others. The concerted modulation of many of these transcripts beforemalignant transformation seems to be conducive to predominantly decrease cell proliferation.This study has revealed candidate key pathways that can be experimentally tested inthe same model system and may constitute novel targets for future translational research.
