High Expression of Induces Tumors Phenotypically Similar to Loss-of-Function Mutations in Mice.

is a negative regulator of p53 and genomic aberrations resulting in increased activity of have been observed in cancers of different origins, indicating that has oncogenic properties. We established a transgenic mouse model overexpressing and showed that these mice developed a wide variety of cancers. -expressing mice developed tumors phenotypically and genetically similar to tumors in mice with dysfunctional p53. T-cell lymphoblastic lymphoma was the most frequent cancer observed in these mice (55%) followed by adenocarcinomas (24%), leukemia (12%) and other solid tumors including neuroblastoma. Characterization of T-cell lymphomas in mice overexpressing demonstrates -deletion and p53-accumulation similar to mice with p53 loss-of-function. Also, mutations which are recurrently observed in T-cell acute lymphoblastic lymphoma (T-ALL) were frequently detected in transgenic mice. Hence, acts as an oncogenic driver in connection with cellular stress, suggesting that the gene status and expression levels should be investigated in wild-type tumors.