Background & Aims:Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH), and were reported to be more resistant to chemically-induced hepatocellu- lar carcinoma (HCC). We investigated the role of c-jun in normal and preneoplastic hepatocyte proliferation induced by ligands of nuclear receptors, which cause liver hyperplasia in the absence of cell loss/death. Methods: The effect of 1,4-bis[2-(3,5-dichloropyridyloxy)]ben- zene (TCPOBOP) on hepatocyte proliferation was determined in c-jun conditional knockout (c-junDli) or in mouse liver where c-jun has been silenced. To study the role of c-jun in HCC devel- opment, c-junDli and WT mice were given diethylnitrosamine (DENA) followed by repeated injections of TCPOBOP. Results: Hepatocyte proliferation induced by TCPOBOP was asso- ciated with a stronger proliferative response and earlier S phase entry in c-junD li mice, compared to WT animals. Moreover, silenc- ing of c-jun in the liver of CD-1 mice caused increased hepatocyte proliferation. A stronger hepatocyte proliferative response of c- junDli mice was observed also following treatment with a ligand of thyroid hormone receptor. Finally, loss of c-jun did not inhibit the development of HCC induced by DENA and promoted by TCPOBOP.
Expression of c-jun acts is not mandatory for mouse hepatocyte proliferation induced by two ligands of nuclear receptors: TCPOBOP and T3.
RAVO, MARIA;WEISZ, Alessandro;
2011-01-01
Abstract
Background & Aims:Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH), and were reported to be more resistant to chemically-induced hepatocellu- lar carcinoma (HCC). We investigated the role of c-jun in normal and preneoplastic hepatocyte proliferation induced by ligands of nuclear receptors, which cause liver hyperplasia in the absence of cell loss/death. Methods: The effect of 1,4-bis[2-(3,5-dichloropyridyloxy)]ben- zene (TCPOBOP) on hepatocyte proliferation was determined in c-jun conditional knockout (c-junDli) or in mouse liver where c-jun has been silenced. To study the role of c-jun in HCC devel- opment, c-junDli and WT mice were given diethylnitrosamine (DENA) followed by repeated injections of TCPOBOP. Results: Hepatocyte proliferation induced by TCPOBOP was asso- ciated with a stronger proliferative response and earlier S phase entry in c-junD li mice, compared to WT animals. Moreover, silenc- ing of c-jun in the liver of CD-1 mice caused increased hepatocyte proliferation. A stronger hepatocyte proliferative response of c- junDli mice was observed also following treatment with a ligand of thyroid hormone receptor. Finally, loss of c-jun did not inhibit the development of HCC induced by DENA and promoted by TCPOBOP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
