0000000000354171
AUTHOR
T Urbanik
showing 6 related works from this author
Bcl-xL and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells
2008
AIM: To explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities. METHODS: Bcl-x(L) and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCR and immunohistochemistry. Bcl-x(L) and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor (EGFR1) antibody, an EGFR1 tyrosine kinase inhibitor, …
Down-regulation of CYLD as a trigger for NF-κB activation and a mechanism of apoptotic resistance in hepatocellular carcinoma cells
2010
The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins. In order to investigate the role of CYLD in apoptotic signaling in human hepatocellular carcinoma (HCC) cells, we first studied the expression levels of CYLD in HCC tissues. CYLD expression was lower in HCC both at protein and mRNA levels compared to the surrounding non-ma…
Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice
2010
Regulation of hepatocellular apoptosis is crucial for liver homeostasis. Increased sensitivity of hepatocytes toward apoptosis results in chronic liver injury, whereas apoptosis resistance is linked to hepatocarcinogenesis and nonresponsiveness to therapy-induced cell death. Recently, we have demonstrated an essential role of the antiapoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) in hepatocyte survival. In mice lacking Mcl-1 specifically in hepatocytes (Mcl-1Δhep), spontaneous apoptosis caused severe liver damage. Here, we demonstrate that chronically increased apoptosis of hepatocytes coincides with strong hepatocyte proliferation resulting in hepatocellular carcinoma (HCC).…
Liver specific deletion of CYLDexon7/8 induces severe biliary damage, fibrosis and increases hepatocarcinogenesis in mice
2012
Background & Aims CYLD is a tumor suppressor gene that is mutated in familial cylindromatosis, an autosomal dominant predisposition to tumors of skin appendages. Reduced CYLD expression has been observed in other tumor entities, including hepatocellular carcinoma. In the present study, we analyzed the role of CYLD in liver homeostasis and hepatocarcinogenesis in vivo . Methods Mice with liver-specific deletion of CYLDexon7/8 ( CYLD FF xAlbCre ) were generated. Liver tissues were histologically analyzed and oval cell activation was investigated. Hepatocarcinogenesis was induced by diethylnitrosamine/phenobarbital (DEN/PB). Microarray expression profiling of livers was performed in untreated …
TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies
2009
AIM: To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors, in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL), on overcoming TRAIL resistance in hepatocellular carcinoma (HCC) and to study the efficacy of agonistic TRAIL antibodies, as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS: Surface expression of TRAIL receptors (TRAIL-R1-4) and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting, respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNA…
Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes
2008
Apoptosis, or programmed cell death, regulates tissue development and homeostasis in multi-cellular organisms. Extrinsic or intrinsic death signals activate pro-apoptotic pathways, resulting in the activation of caspases and finally in cell death. An important event during apoptosis process is the permeabilization of the outer mitochondrial membrane (OMM). Integrity of the OMM is regulated by the Bcl-2 protein family, which is divided into three groups: anti-apoptotic members Bcl-2, Bcl-xL and myeloid cell leukemia-1 (Mcl-1), pro-apoptotic multidomain members Bax and Bak, and pro-apoptotic BH3-only proteins. Mitochondrial activation is regulated by selective interactions of Bcl-2 proteins v…