The BH3-only protein BID impairs the p38-mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice.

Orlik, Johanna; Schüngel, Sven; Buitrago-Molina, Laura Elisa; Marhenke, Silke; Geffers, Robert; Endig, Jessica; Lobschat, Katharina; Rössler, Stephanie; Goeppert, Benjamin; Manns, Michael P; Gross, Atan; Vogel, Arndt

dc.contributor.author	Orlik, Johanna
dc.contributor.author	Schüngel, Sven
dc.contributor.author	Buitrago-Molina, Laura Elisa
dc.contributor.author	Marhenke, Silke
dc.contributor.author	Geffers, Robert
dc.contributor.author	Endig, Jessica
dc.contributor.author	Lobschat, Katharina
dc.contributor.author	Rössler, Stephanie
dc.contributor.author	Goeppert, Benjamin
dc.contributor.author	Manns, Michael P
dc.contributor.author	Gross, Atan
dc.contributor.author	Vogel, Arndt
dc.date.accessioned	2015-09-14T14:29:36Z	en
dc.date.available	2015-09-14T14:29:36Z	en
dc.date.issued	2015-09	en
dc.identifier.citation	The BH3-only protein BID impairs the p38-mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice. 2015, 62 (3):816-28 Hepatology	en
dc.identifier.issn	1527-3350	en
dc.identifier.pmid	25951810	en
dc.identifier.doi	10.1002/hep.27888	en
dc.identifier.uri	http://hdl.handle.net/10033/577244	en
dc.description.abstract	Apoptosis is critical for maintaining tissue homeostasis, and apoptosis evasion is considered as a hallmark of cancer. However, increasing evidence also suggests that proapoptotic molecules can contribute to the development of cancer, including liver cancer. The aim of this study was to further clarify the role of the proapoptotic B-cell lymphoma 2 homology domain 3 (BH3)-only protein BH3 interacting-domain death agonist (BID) for chronic liver injury (CLI) and hepatocarcinogenesis (HCG). Loss of BID significantly delayed tumor development in two mouse models of Fah-mediated and HBsTg-driven HCG, suggesting a tumor-promoting effect of BID. Liver injury as well as basal and mitogen-stimulated hepatocyte proliferation were not modulated by BID. Moreover, there was no in vivo or in vitro evidence that BID was involved in DNA damage response in hepatocytes and hepatoma cells. Our data revealed that CLI was associated with strong activation of oxidative stress (OS) response and that BID impaired full activation of p38 after OS.
dc.language.iso	en	en
dc.title	The BH3-only protein BID impairs the p38-mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice.	en
dc.type	Article	en
dc.contributor.department	Hannover Medical School, Hannover, Germany.	en
dc.identifier.journal	Hepatology (Baltimore, Md.)	en
refterms.dateFOA	2016-07-15T00:00:00Z
html.description.abstract	Apoptosis is critical for maintaining tissue homeostasis, and apoptosis evasion is considered as a hallmark of cancer. However, increasing evidence also suggests that proapoptotic molecules can contribute to the development of cancer, including liver cancer. The aim of this study was to further clarify the role of the proapoptotic B-cell lymphoma 2 homology domain 3 (BH3)-only protein BH3 interacting-domain death agonist (BID) for chronic liver injury (CLI) and hepatocarcinogenesis (HCG). Loss of BID significantly delayed tumor development in two mouse models of Fah-mediated and HBsTg-driven HCG, suggesting a tumor-promoting effect of BID. Liver injury as well as basal and mitogen-stimulated hepatocyte proliferation were not modulated by BID. Moreover, there was no in vivo or in vitro evidence that BID was involved in DNA damage response in hepatocytes and hepatoma cells. Our data revealed that CLI was associated with strong activation of oxidative stress (OS) response and that BID impaired full activation of p38 after OS.