Telomerase deletion limits progression of p53-mutant hepatocellular carcinoma with short telomeres in chronic liver disease.

Background & Aims: During early stages of carcinogenesis most human epithelial cancers including hepatocellular carcinoma (HCC) have been observed to transit through a "crisis" stage characterized by telomere shortening, loss of p53 checkpoint function, and a sharp increase in aneuploidy. The function of telomerase during in vivo hepatocarcinogenesis has not been studied in this genetic context.

Methods: Here we generated a mouse model in which HCC was induced by chronic organ damage (HBs-AG transgene) in the presence of telomere shortening and p53 deletion.

Specific ablation of the transcription factor CREB in sympathetic neurons surprisingly protects against developmentally regulated apoptosis.

The cyclic-AMP response element-binding (CREB) protein family of transcription factors plays a crucial role in supporting the survival of neurons. However, a cell-autonomous role has not been addressed in vivo. To investigate the cell-specific role of CREB, we used as a model developing sympathetic neurons, whose survival in vitro is dependent on CREB activity.