Resistance to Carcinogenesis in the African Spiny Mouse (Acomys) correlates with upregulation of tumor suppressor genes.

Abstract

Cancer remains a leading cause of morbidity and mortality worldwide, driving extensive research into the mechanisms that contribute to its development and progression. The search for animal models capable of shedding light on mechanisms of cancer resistance has led researchers to explore various rodent species. Among these, the African Spiny Mouse (Acomys sp.) has attracted considerable attention due to its regenerative abilities. In our study, we compared the response of Mus musculus and Acomys dimidiatus mice to treatment with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) combined with the inducer of proliferation 12-O-tetradecanoylphorbol-13-acetate (TPA). While both Acomys and Mus mice experienced carcinogenic damage to their skin cells, mounted proliferative responses and underwent immune cell infiltration, only Mus mice developed tumors, whereas Acomys remained tumor-free. To uncover the molecular mechanisms underlying this resistance, we performed RNA sequencing on tissue samples from both species at baseline and at multiple time points during the carcinogenesis protocol. The data reveal distinctly different transcriptional responses between both species. In particular, Acomys showed massive upregulation of immune related genes, including a set of tumor suppressor genes, while Mus seemed to focus its response on modifying epidermis structure and regulation of the cell cycle. These differences correlated with an increased apoptotic response in Acomys but not Mus. In summary, our study provides compelling evidence that Acomys mice exhibit remarkable resistance to tumor development under DMBA/TPA carcinogen treatment mediated through the upregulation of a range of processes related to immune surveillance.