Telomerase promotes Hepatocarcinogenesis in the context of p53- and Telomerase-Dysfunction by limiting Chromosomal Instability
A Lechel, H Holstege, Y Begus, A Schienke, K Kamino, U Lehmann, J Buer, J Buer, MP Manns, S Kubicka, P Schirrmacher, J Jonkers, P Schirrmacher, KL Rudolph · Zeitschrift für Gastroenterologie · 2006 · Heft 01
Bibliografische Angaben
Zusammenfassung
Telomere shortening and p53 deletion cooperatively induce chromosomal instability and cancer initiation at the crisis stage, but the role of telomerase in this scenario remains to be defined. We generated a humanized mouse model in which hepatocellular cancer (HCC) was induced by chronic liver damage, telomere shortening, and targeted p53 deletion in mouse liver. In this model HCC developed at an age of 12–15 months and exhibited high rates of chromosomal instability similar to human HCC. Importantly, the formation of HCC was strongly suppressed in mice lacking telomerase (mTERC-/-) compared to siblings that wer…
