The Rgr oncogene induces tumorigenesis in transgenic mice

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 17; pp. 6041 - 6049
• Main Authors: JIMENEZ, Maria, PEREZ DE CASTRO, Ignacio, BENET, Marta, GARCIA, Juan F, INGHIRAMI, Giorgio, PELLICER, Angel
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2004
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; CD4 Antigens - genetics; Cell Cycle Proteins - genetics; Cell Transformation, Neoplastic - genetics; Cyclin-Dependent Kinase Inhibitor p15; Disease Progression; Female; Lymphoma, T-Cell - genetics; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; NIH 3T3 Cells; Pharmacology. Drug treatments; ral Guanine Nucleotide Exchange Factor - genetics; Transfection; Tumor Suppressor Proteins - genetics; Tumors; Vertebrata; Mammalia; Mouse; Rodentia; Transgenic animal; Onc gene; Carcinogenesis
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-03-3389

To study the oncogenic potential of Rgr in vivo, we have generated several transgenic Rgr mouse lines, which express the oncogene under the control of different promoters. These studies revealed that Rgr expression leads to the generation of various pathological alterations, including fibrosarcomas, when its transgenic expression is restricted to nonlymphoid tissues. Moreover, the overall incidence and latency of fibrosarcomas were substantially increased and shortened, respectively, in a p15INK4b-defective background. More importantly, we also have demonstrated that Rgr expression in thymocytes of transgenic mice induces severe alterations in the development of the thymocytes, which eventually lead to a high incidence of thymic lymphomas. This study demonstrates that oncogenic Rgr can induce expression of p15INK4b and, more importantly, that both Rgr and p15INK4b cooperate in the malignant phenotype in vivo. These findings provide new insights into the tumorigenic role of Rgr as a potent oncogene and show that p15INK4b can act as a tumor suppressor gene.