Is Cdt1 an oncogene?
It has been reported that Cdt1 overexpression endows murine NIH3T3 cells with the capacity to form tumors in nude mice [76]. However, in Rat-1, another cell line commonly used to estimate transformation potency of classical oncogenes, no transformed phenotype was observed with stable overexpression of Cdt1 [22]. This difference might simply be attributable to cell type-specific responses. However, there is abundant evidence that deregulation of Cdt1 impacts on cells by inducing re-replication, chromosomal damage, and genomic instability [9,22]. Thus, I prefer the explanation that deregulated Cdt1 does not lead to acute oncogenic transformation, but rather to chronic chromosomal damage and instability that eventually results in transformation. In fact, Cdt1 overexpression in transgenic thymocytes by itself does not lead to tumor formation but modulates and enhances tumor formation induced by p53 deficiency [77]. Importantly, Cdt1 protein is actually overexpressed in human cancer cells [
