The expression of p53-target genes in the hypoxia-tolerant subterranean mole-rat is hypoxia-dependent and similar to expression patterns in solid tumors

Band, Mark; Ashur‐Fabian, Osnat; Avivi, Aaron

doi:10.4161/cc.9.16.12712

Cited by 17 publications

(13 citation statements)

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“…These genes include important transcription factors, such as p53 and its downstream genes (Ashur-Fabian et al, 2004;Avivi et al, 2007;Band et al, 2010), metabolically important genes (Avivi et al, 1999Band et al, 2009;Shams et al, 2004Shams et al, , 2005c and their receptors (Band et al, 2008;Ravid et al, 2007;Shams et al, 2005b). We conclude that adaptation at the level of gene regulation has a major influence on Spalax evolution.…”

Section: Antioxidant Gene Expression Is Constitutively Elevated In Spmentioning

confidence: 93%

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Schülke

Dreidax

Malik

et al. 2012

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Section: Antioxidant Gene Expression Is Constitutively Elevated In Spmentioning

confidence: 93%

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Schülke

Dreidax

Malik

et al. 2012

Gene

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“…Accordingly, it appears that hypoxia induced apoptosis is tightly controlled, and possibly restricted in Spalax . Similarly, previous studies suggested that critical p53 hypoxia induced apoptotic pathways are blocked in Spalax [15,16]. Also, the accepted functions assigned to genes among the common databases may not reflect the true functions of homologues in all organisms, for example, the p53 pathway as mentioned above.…”

Section: Discussionmentioning

confidence: 94%

Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

et al. 2012

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BackgroundThe development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research.ResultsUsing microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals.ConclusionsThis is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to medical research.

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“…Furthermore, patterns of expression in many tumor types resemble those found normally in Spalax . For example, in both cases there is an over-expression of p53 associated genes that enable the cell to escape hypoxia induced apoptosis by favoring reversible cell cycle arrest [15]–[17]. Accordingly, the binding domain of Spalax p53 harbors two amino acid substitutions identical to those found in p53 expressed in human tumor cells, resulting in increased activation of DNA repair elements and reduced activation of apoptotic genes [15].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Sequencing of the Blind Subterranean Mole Rat, Spalax galili: Utility and Potential for the Discovery of Novel Evolutionary Patterns

et al. 2011

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The blind subterranean mole rat (Spalax ehrenbergi superspecies) is a model animal for survival under extreme environments due to its ability to live in underground habitats under severe hypoxic stress and darkness. Here we report the transcriptome sequencing of Spalax galili, a chromosomal type of S. ehrenbergi. cDNA pools from muscle and brain tissues isolated from animals exposed to hypoxic and normoxic conditions were sequenced using Sanger, GS FLX, and GS FLX Titanium technologies. Assembly of the sequences yielded over 51,000 isotigs with homology to ∼12,000 mouse, rat or human genes. Based on these results, it was possible to detect large numbers of splice variants, SNPs, and novel transcribed regions. In addition, multiple differential expression patterns were detected between tissues and treatments. The results presented here will serve as a valuable resource for future studies aimed at identifying genes and gene regions evolved during the adaptive radiation associated with underground life of the blind mole rat.

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The expression of p53-target genes in the hypoxia-tolerant subterranean mole-rat is hypoxia-dependent and similar to expression patterns in solid tumors

Cited by 17 publications

References 50 publications

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

Transcriptome Sequencing of the Blind Subterranean Mole Rat, Spalax galili: Utility and Potential for the Discovery of Novel Evolutionary Patterns

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