RB depletion is required for the continuous growth of tumors initiated by loss of RB

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.

Automated summary

The RB tumor suppressor is inactivated in various human tumors promoting tumorigenesis. A new mouse model was used to study the consequences of RB depletion and re-activation, showing that continuous RB loss is required for maintaining tumor phenotypes and re-expressing RB leads to cell cycle arrest in cancer cells.