Meeting Abstract
Previous work has suggested a link between the biological processes underlying regeneration and those underlying cancer. The tumor suppressor protein P53 is mutated in the majority of tumors and has recently been implicated in playing a role in tissue plasticity. We compared the effect of inhibition and stabilization of p53 on tail regeneration in axolotls (Ambystoma mexicanum) and zebrafish (Danio rerio). All fish treatment groups regenerated tail fins, but regenerative outgrowth was slightly diminished and endothelial sprouting occurred earlier in tp53 mutant fish and those treated with the p53 inhibitor pifithrin-alpha. The effect was reversible with washout of the inhibitor. In contrast, p53 inhibition in salamanders eliminated regenerative outgrowth of the tail and the effect was not reversible with washout of the inhibitor. The effects of the p53 stabilizer nutlin on tail regeneration were more modest. Our results provide evidence that the effect of p53 inhibition by pifithrin on tail regeneration in ectothermic vertebrates is species- and tissue-specific. We are continuing to analyze the effects of p53 alteration on regeneration at the histological level. This work will give us a broader understanding of how tumor suppressors exert their effects within different non-cancerous but proliferative tissue environments.
