జర్నల్ ఆఫ్ కార్సినోజెనిసిస్ & మ్యూటాజెనిసిస్

నైరూప్య

Pim1 Kinase Cooperates with Hormone Treatment to Promote Bladder and Ureteral Urothelial Hyperplasia

Maja Narlik-Grassow, Carmen Blanco-Aparicio, Yolanda Cecilia, Marco Perez, Sandra Muñoz-Galvan, Marta Cañamero, Oliver Renner and Amancio Carnero

The Pim serine/threonine kinases have been shown to be overexpressed in cancer. Elevated levels of Pim1 kinase were demonstrated in human leukemia and lymphomas, as well as in solid tumors such as pancreatic, prostate and bladder cancers, and have been proposed as a prognostic marker. Although the Pim kinases have been identified as oncogenes in transgenic mouse models, they have only weak transforming abilities on their own. However, they have been shown to greatly enhance the ability of other genes or chemical carcinogens to induce tumors. To explore the role of Pim1 in bladder and ureteral urothelial cancer, we generated a conditional Pim1 transgenic mouse model and found that prostate specific antigen-(PSA)-driven Cre expression lead to transgene expression in the bladder upon (testosterone/estrogen) hormone treatment. We then explored the effect of Pim1 overexpression on hormone treatment, either alone or in combination with Pten haploinsufficiency. We found that Pim1 overexpression increased the severity of bladder and ureteral urothelial hyperplasias in both backgrounds, leading to pyelonephritis in transgenic animals. Our data suggest that Pim1 might contribute to progression, rather than initiation, and that the hyperplasias also contribute to the development of pyelonephritis.