PMID- 12821940
OWN - NLM
STAT- MEDLINE
DCOM- 20030718
LR  - 20120604
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 26
DP  - 2003 Jun 26
TI  - Hepatocyte growth factor induces apoptosis through the extrinsic pathway in 
      hepatoma cells: favouring role of hypoxia-inducible factor-1 deficiency.
PG  - 4062-73
AB  - Two hepatocarcinoma cell lines, the Hepa-1 wild-type (c1c7) and the beta-subunit 
      mutated (c4) lacking hypoxia-inducible factor-1 (HIF-1) activity, were 
      differentially susceptible to apoptosis by hepatocyte growth factor (HGF). The c4 
      cells were 40% apoptotic 48 h after HGF treatment. On the contrary, the wild-type 
      c1c7 cells showed modest signs of apoptosis only at 72 h. The revertant vT[2] 
      cells, consisting of c4 cells stably transfected with HIF-1beta expression 
      vector, behaved as the parental cells. To understand the mechanisms of this 
      different sensitivity, we examined a panel of genes involved in apoptosis: 
      ornithine decarboxylase, c-Myc and p53 protein levels progressively decreased 
      while JNK1, caspase 8 and 3 activities persistently increased in c4 cells 
      undergoing apoptosis. Distinct time-related events in c1c7 cells were the 
      transient activations of JNK1 and caspase 8 followed by the accumulation of ODC 
      and c-Myc proteins. The proapoptotic effect of HGF in c4 hepatocarcinoma cells 
      seems to be related to HIF-1 deficiency with loss of cytoprotective and 
      signalling functions. This may contribute to the triggering of the extrinsic 
      pathway consisting in caspase 8 activation, which in turn causes BID cleavage and 
      cytochrome c release. The effector caspase 3 is also activated.
FAU - Matteucci, Emanuela
AU  - Matteucci E
AD  - Institute of General Pathology, School of Medicine, University of Milano, via L. 
      Mangiagalli, 31-20133 Milano, Italy.
FAU - Modora, Silvia
AU  - Modora S
FAU - Simone, Matteo
AU  - Simone M
FAU - Desiderio, Maria Alfonsina
AU  - Desiderio MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cadherins)
RN  - 0 (Cytochrome c Group)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Apoptosis
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cadherins/metabolism
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Caspase 3
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Cell Death
MH  - Cytochrome c Group/metabolism
MH  - DNA-Binding Proteins/*genetics/*physiology
MH  - Densitometry
MH  - Enzyme Activation
MH  - Genetic Vectors
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mitochondria/metabolism
MH  - Mitogen-Activated Protein Kinase 8
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation
MH  - Nuclear Proteins/*genetics/*physiology
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-met
MH  - *Receptors, Growth Factor
MH  - Scattering, Radiation
MH  - Time Factors
MH  - Trans-Activators/metabolism
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
EDAT- 2003/06/25 05:00
MHDA- 2003/07/19 05:00
CRDT- 2003/06/25 05:00
PHST- 2003/06/25 05:00 [pubmed]
PHST- 2003/07/19 05:00 [medline]
PHST- 2003/06/25 05:00 [entrez]
AID - 1206519 [pii]
AID - 10.1038/sj.onc.1206519 [doi]
PST - ppublish
SO  - Oncogene. 2003 Jun 26;22(26):4062-73. doi: 10.1038/sj.onc.1206519.