2026-04-27T02:05:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/67422024-11-29T13:51:19Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Ferrara Romeo, Iole
author
Martinez Rodriguez, Paula
author
Blasco , MA
funder
Ministerio de Economía y Competitividad (España)
2018-11-29T12:03:23Z
2018-11-29T12:03:23Z
2018-10-11
PLoS One. 2018; 13 (10): e0204909.
1932-6203
http://hdl.handle.net/20.500.12105/6742
30307978
10.1371/journal.pone.0204909
1932-6203
PloS one
RAP1, a component of the telomere-protective shelterin complex, has been shown to have both telomeric and non-telomeric roles. In the liver, RAP1 is involved in the regulation of metabolic transcriptional programs. RAP1-deficient mice develop obesity and hepatic steatosis, these phenotypes being more severe in females than in males. As hepatic steatosis and obesity have been related to increased liver cancer in mice and humans, we set out to address whether RAP1 deficiency resulted in increased liver cancer upon chemical liver carcinogenesis. We found that Rap1-/- females were more susceptible to DEN-induced liver damage and hepatocellular carcinoma (HCC). DEN-treated Rap1-/- female livers showed an earlier onset of both premalignant and malignant liver lesions, which were characterized by increased abundance of γH2AX-positive cells, increased proliferation and shorter telomeres. These findings highlight an important role for RAP1 in protection from liver damage and liver cancer.
eng
PROLIFERATOR-ACTIVATED RECEPTOR
GENE-EXPRESSION
TELOMERE DYSFUNCTION
MAMMALIAN TELOMERES
METABOLIC SYNDROME
LIPID HOMEOSTASIS
PPAR-ALPHA
LIVER
CARCINOGENESIS
HEPATOCARCINOGENESIS
Mice lacking RAP1 show early onset and higher rates of DEN-induced hepatocellular carcinomas in female mice
journal article
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URL
https://repisalud.isciii.es/bitstreams/cc1dac0b-9ac8-4b7c-9bef-0d813db36946/download
File
MD5
804dc01b73cc960c8fb1085ec9293fe7
10305337
application/pdf
MicelackingRAP1show_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/bebdb033-767e-4821-92a3-bdd942d66936/download
File
MD5
638bb8bd4a3c4a22aace99cc615d60de
56528
text/plain
MicelackingRAP1show_2018.pdf.txt