Naked Mole-Rat Cells are Susceptible to Malignant Transformation by <i>SV40LT</i> and Oncogenic Ras

Abstract The Naked Mole-Rat, Hetercephalus glaber , is a mouse-sized subterranean rodent native to East Africa. Research on NMRs is intensifying in an effort to gain leverage from their unusual physiology, long-life span and cancer resistance. Few studies have attempted to explain the reasons behind NMRs cancer resistance, but most prominently Tian et al. reported that NMR cells produce high-molecular weight hyaluronan as a potential cause for the NMR’s cancer resistance. Tian et al. have shown that NMR cells are resistant to transformation by SV40 Large T Antigen ( SV40LT ) and oncogenic HRAS ( HRAS G12V ), a combination of oncogenes sufficient to transform mouse and rat fibroblasts. We have developed a single lentiviral vector to deliver both these oncogenes and generated multiple cell lines from five different tissues and nine different NMRs, and report here that contrary to Tian et al.’s observation, NMR cells are susceptible to oncogenic transformation by SV40LT and HRAS . Our data thus point to a non-cell autonomous mechanism underlying the remarkable cancer resistance of NMRs. Identifying these non-cell autonomous mechanisms could have implications on our understanding of human cancer development.