Elephant Tp53 (Ep53) Retrogene Protein Expression Enhances Cellular Apoptosis In Response To Dna Damage

We previously reported that compared with other mammalian species, elephants have a lower than expected rate of cancer (Abegglen JAMA 2015). While exploring cancer resistance in elephants, we discovered that elephants have 20 copies of TP53 (1 ancestral gene with introns and 19 retrogenes) compared to humans with 1 copy. TP53 amplification was associated with increased p53-mediated apoptosis induced by DNA damage in elephant cells compared to human cells. As a follow up to this study, we further explored the function of these elephant TP53 retrogenes by expressing their protein (ep53) in cells with 2 functional TP53 alleles. NIH/3T3 cells were transfected with a mammalian expression construct encoding TP53 retrogene 9 fused to an epitope tag (myc). Western blot analysis probing for myc confirmed expression of retrogene 9. To measure the functional consequence of expression, we compared apoptosis of cells transfected with empty vector to cells transfected with myc-tagged retrogene 9 after doxorubicin treatment. Apoptosis was measured with a triplex assay that assesses viability, cytotoxicity and apoptosis (Apo Tox-Glo, Promega). We observed a significant increase in apoptosis of NIH/3T3 cells expressing retrogene 9 compared to empty vector transfected control cells (10μM doxorubicin, P Citation Format: Lisa M. Abegglen, Rosann Robinson, Lauren Donovan, Aleah F. Caulin, Mor Goldfeder, Avi Schroeder, Carlo C. Maley, Joshua D. Schiffman. Elephant TP53 (ep53) retrogene protein expression enhances cellular apoptosis in response to DNA damage. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3686.