2004
DOI: 10.1038/sj.onc.1208308
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Contrasting effects of telomere shortening on organ homeostasis, tumor suppression, and survival during chronic liver damage

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Cited by 23 publications
(20 citation statements)
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“…In previous work using the mouse telomerase RNA component (mTerc) knockout, we addressed the role of telomeres in hepatocarcinogenesis and showed that telomere dysfunction enhanced initiation of hepatic neoplasms yet impaired full malignant progression of these lesions (12). Similarly, Rudolph et al have shown that hepatocellular carcinoma in a Hepatitis B virus surface antigen transgenic model is suppressed in telomerase-deficient mice with short telomeres (13). Collectively, these results support the view that telomere-induced genomic instability can initiate hepatic neoplasias, but this mechanism alone is insufficient to drive progression to advanced hepatocellular carcinomas.…”
Section: Introductionsupporting
confidence: 74%
“…In previous work using the mouse telomerase RNA component (mTerc) knockout, we addressed the role of telomeres in hepatocarcinogenesis and showed that telomere dysfunction enhanced initiation of hepatic neoplasms yet impaired full malignant progression of these lesions (12). Similarly, Rudolph et al have shown that hepatocellular carcinoma in a Hepatitis B virus surface antigen transgenic model is suppressed in telomerase-deficient mice with short telomeres (13). Collectively, these results support the view that telomere-induced genomic instability can initiate hepatic neoplasias, but this mechanism alone is insufficient to drive progression to advanced hepatocellular carcinomas.…”
Section: Introductionsupporting
confidence: 74%
“…Cirrhosis from any etiology, including CC, is another local fibrotic disease with systemic implications and, thus, is expected to cause telomere shortening, as indeed was demonstrated previously [Wiemann et al, 2002;Chaiteerakij and Roberts, 2011]. Finally, CC, the premalignant state of HCC, can theoretically be associated with telomere dysfunction and repression of telomerase since these changes were demonstrated in both mouse models [Wiemann et al, 2005] and in human subjects with HBV-associated HCC [Plentz et al, 2004;Kim et al, 2009].…”
Section: Discussionmentioning
confidence: 85%
“…Similarly, Wiemann et al utilised a late generation telomerase knockout model to demonstrate that mice with short hepatocyte telomeres had decreased survival when subjected to chronic liver injury [78]; mice with short telomeres (induced through telomerase knockout) and chronic liver damage (induced by hepatocyte specific expression of HBV surface antigen under an albumin promoter) had reduced survival when compared to litter-mates with longer telomeres [78]. Notably however, mice with short telomeres showed strong inhibition of HCC formation emphasising the dual role of telomere shortening.…”
Section: Telomeres In Chronic Liver Diseasementioning
confidence: 97%
“…The beneficial effects of the intact telomere/telomerase system have been demonstrated with suppression of the development of HCC in a mouse model [78]. Utilising a telomerase knock-out mouse model, Wiemann et al demonstrated that short hepatocyte telomeres were associated with marked inhibition of HCC formation in a late generation telomerase knock-out mouse model [78].…”
Section: Telomeres In Hccmentioning
confidence: 97%