Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/21143
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Title

High sensitivity to carcinogens in the brain of a mouse model of Alzheimer's disease

AuthorsSerrano, Julia CSIC; Fernández Fernández, Ana Patricia CSIC ORCID; Martínez-Murillo, Ricardo CSIC ORCID; Martínez, Alfredo
KeywordsBrain tumors
Alzheimer’s disease
Tumor microenvironment
Inflammatory mediators1
Carcinogenesis
Issue Date25-Jan-2010
PublisherNature Publishing Group
CitationOncogene 1-7 (2010)
AbstractCancer and Alzheimer’s disease (AD) are commonly found among elderly patients. Chronic inflammation is the characteristic of both diseases. Amyloid-b peptide is the main inducer of inflammation in AD. Moreover, chronic inflammation promotes cancer, suggesting that AD patients may be more prone to develop cancer than nondemented people. To test this hypothesis, we injected the carcinogen 20-methylcholanthrene in the brain of transgenic mice overexpressing the mutant forms of amyloid precursor protein (APP) and presenilin 1 (PS1), as a model of AD, and their wild-type (WT) littermates. Mutant mice developed tumors faster and with higher incidence than their WT counterparts. Expression of the inflammatory markers interleukin (IL)-1a, IL-1b, IL-6, IP-10 and tumor necrosis factor-a (TNF-a) was measured in AD and WT mice of 3 and 12 months of age that had not been exposed to the carcinogen. These cytokines were elevated in older AD mice, indicating the existence of a highly inflammatory milieu in these animals. We also found elevated expression of a mutated form of p53 in older AD mice, suggesting an alternative mechanism for the predisposition of AD brains to develop brain tumors. Clinical studies reporting comorbidity of AD and brain cancer are needed to understand whether our observations hold true for humans.
Publisher version (URL)http://dx.doi.org/10.1038/onc.2009.503
URIhttp://hdl.handle.net/10261/21143
DOI10.1038/onc.2009.503
ISSN0950-9232
Appears in Collections:(IC) Artículos

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