PMID- 11571297
OWN - NLM
STAT- MEDLINE
DCOM- 20020124
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 50
DP  - 2001 Dec 14
TI  - Hepatocyte growth factor/scatter factor blocks the mitochondrial pathway of 
      apoptosis signaling in breast cancer cells.
PG  - 47257-65
AB  - The cytokine hepatocyte growth factor/scatter factor (HGF/SF) has been found to 
      protect a variety of epithelial and cancer cell types against cytotoxicity and 
      apoptosis induced by DNA damage, but the specific apoptotic signaling events and 
      the levels at which they are blocked by HGF/SF have not been identified. We found 
      that treatment of MDA-MB-453 human breast cancer cells with adriamycin (also 
      known as doxorubicin, a DNA topoisomerase IIalpha inhibitor) induced a series of 
      time-dependent events, including the mitochondrial release of cytochrome c and 
      apoptosis-inducing factor, mitochondrial membrane depolarization, activation of a 
      set of caspases (caspase-9, -3, -7, -2, and -8), cleavage of poly(ADP-ribose) 
      polymerase (PARP), and up-regulation of expression of the Fas ligand. All of 
      these events were blocked by preincubation of the cells with HGF/SF. In contrast, 
      the pan-caspase inhibitor benzyloxycarbonyl-VAD-fluoromethylketone blocked some 
      of these events (e.g. caspase-3 activation and PARP cleavage) but did not block 
      cytochrome c release or mitochondrial depolarization. These findings suggest that 
      HGF/SF functions, in part, upstream of the mitochondria to block mitochondrial 
      apoptosis signaling, prevent activation of multiple caspases, and protect breast 
      cancer cells against apoptosis.
FAU - Gao, M
AU  - Gao M
AD  - Department of Radiation Oncology, Long Island Jewish Medical Center, Long Island 
      Campus for the Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
FAU - Fan, S
AU  - Fan S
FAU - Goldberg, I D
AU  - Goldberg ID
FAU - Laterra, J
AU  - Laterra J
FAU - Kitsis, R N
AU  - Kitsis RN
FAU - Rosen, E M
AU  - Rosen EM
LA  - eng
GR  - R01-80000/PHS HHS/United States
GR  - R01-82599/PHS HHS/United States
GR  - R01-ES 09169/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010924
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (AIFM1 protein, human)
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Inducing Factor)
RN  - 0 (Coloring Agents)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Flavoproteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 80168379AG (Doxorubicin)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - *Apoptosis
MH  - Apoptosis Inducing Factor
MH  - Breast Neoplasms/*metabolism
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Coloring Agents/pharmacology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Cytochrome c Group/metabolism
MH  - Doxorubicin/pharmacology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Fas Ligand Protein
MH  - Flavoproteins/metabolism
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Potentials
MH  - Membrane Proteins/metabolism
MH  - Mitochondria/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
MH  - Tetrazolium Salts/pharmacology
MH  - Thiazoles/pharmacology
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2001/09/26 10:00
MHDA- 2002/01/25 10:01
CRDT- 2001/09/26 10:00
PHST- 2001/09/26 10:00 [pubmed]
PHST- 2002/01/25 10:01 [medline]
PHST- 2001/09/26 10:00 [entrez]
AID - S0021-9258(19)37260-6 [pii]
AID - 10.1074/jbc.M106791200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Dec 14;276(50):47257-65. doi: 10.1074/jbc.M106791200. Epub 2001 
      Sep 24.