Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+-liver cells deficient for p53 and Rb

Simple item page
dc.contributor.authorMatondo, R. B.
dc.contributor.authorToussaint, M. J. M.
dc.contributor.authorGovaert, K.M.
dc.contributor.authorVuuren, L. D.
dc.contributor.authorNantasanti, S.
dc.contributor.authorNijkamp, M. W.
dc.contributor.authorPandit, S. K.
dc.contributor.authorTooten, P. C. J.
dc.contributor.authorKoster, M. H.
dc.contributor.authorHolleman, K.
dc.contributor.authorSchot, A.
dc.contributor.authorGu, G.
dc.contributor.authorSpee, B.
dc.contributor.authorRoskams, T.
dc.contributor.authorBorel, R. I.
dc.contributor.authorSchotanus, B.
dc.contributor.authorKranenburg, O.
dc.contributor.authorde Bruin, A.
dc.date.accessioned2018-10-09T06:23:14Z
dc.date.available2018-10-09T06:23:14Z
dc.date.issued2016-08-23
dc.description.abstractThe long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis. We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/ liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice. We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin- 19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells. These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site.en_US
dc.description.sponsorshipNFP grant : R.B.M., DU.282001.1.3en_US
dc.identifier.otherPMID: 27323406
dc.identifier.urihttps://www.suaire.sua.ac.tz/handle/123456789/2616
dc.language.isoenen_US
dc.subjectLiveren_US
dc.subjectHCCen_US
dc.subjectHepatocyteen_US
dc.subjectHepatitisen_US
dc.subjectHepatectomyen_US
dc.subjectTumoren_US
dc.subjectRben_US
dc.subjectp53en_US
dc.titleSurgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+-liver cells deficient for p53 and Rben_US
dc.typeArticleen_US
dc.urlhttps://doi.org/10.18632/oncotarget.9952en_US

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Matondo_JCI85506.pdf
Size:
6.89 MB
Format:
Adobe Portable Document Format
Description:
Main article and supporting information
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.66 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Other documents (eg. Reports, Presentations)