Real-time in vivo imaging of p16Ink4agene expression: A new approach to study senescence stress signaling in living animals

Abstract

Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16INK4a. To date, much of our current knowledge of how human p16INK4agene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16INK4agene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16INK4agene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. To eliminate any potential problems arising from tissue culture imposed stress, we have recently developed a bioluminescence imaging (BLI) system for non-invasive and real-time analysis of human p16INK4agene expression in the context of a living animal. Here, we discuss the molecular mechanisms that direct p16INK4agene expression in vivoand its potential for tumor suppression.© 2010 Ohtani et al; licensee BioMed Central Ltd.