Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism
Language: 
English
Abstract: 

Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7-20 population doublings, after which the cells began secreting IFN-?, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-?. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground.

Author(s): 
Gorbunova, Vera
Hine, Christopher
Tian, Xiao
Ablaeva, Julia
Gudkov, Andrei V.
Nevo, Eviatar
Seluanov, Andrei
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
11/20/2012
Publication Year: 
2012
Pages: 
19392-19396
Volume: 
109
Issue: 
47
ISSN: 
1091-6490
DOI: 
10.1073/pnas.1217211109
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23129611 PMCID: PMC3511137

Turabian/Chicago Citation

Vera Gorbunova, Christopher Hine, Xiao Tian, Julia Ablaeva, Andrei V. Gudkov, Eviatar Nevo and Andrei Seluanov. 11/20/2012. "Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism." Proceedings of the National Academy of Sciences of the United States of America 109: 47: 19392-19396. 10.1073/pnas.1217211109.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.1217211109 | issn = 1091-6490 | volume = 109 | pages = 19392-19396 | last = Gorbunova | first = Vera | coauthors = Hine, Christopher, Tian, Xiao, Ablaeva, Julia, Gudkov, Andrei V., Nevo, Eviatar, Seluanov, Andrei | title = Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 11/20/2012 | pmid = | pmc = }} </ref>