PMID- 16053510
OWN - NLM
STAT- MEDLINE
DCOM- 20050921
LR  - 20220408
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 96
IP  - 7
DP  - 2005 Jul
TI  - Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in 
      squamous cell carcinoma cells.
PG  - 394-402
AB  - The transcriptional factor hypoxia-inducible factor-1 (HIF-1) plays an important 
      role in solid tumor cell growth and survival. Overexpression of HIF-1alpha has 
      been demonstrated in many human tumors and predicts a poor response to 
      chemoradiotherapy. We examined the HIF-1alpha-induced survival pathways in human 
      oral squamous cell carcinoma cell (OSCC) lines. The results showed that forced 
      expression of HIF-1alpha suppressed hypoxia-induced apoptosis of OSCC lines by 
      inhibiting cytochrome c release from mitochondria. Overexpression of HIF-1alpha 
      inhibited the generation of reactive oxygen species (ROS), elevation of 
      intracellular Ca(2+) concentration, reduction of mitochondrial membrane 
      potential, and cytosolic accumulation of cytochrome c, which resulted in the 
      inactivation of caspase-9 and caspase-3. In addition, antiapoptotic Bcl-2 and 
      Bcl-X(L) levels were increased and pro-apoptotic Bax and Bak levels were 
      decreased in the HIF-1alpha-overexpressing OSCC line. Overexpression of 
      HIF-1alpha also increased the levels of phosphorylation of Akt and extracellular 
      signal-regulated kinases (ERK). These findings indicate that HIF-1alpha prevents 
      apoptotic cell death through two mechanisms, including inhibition of cytochrome c 
      release and activation of Akt and ERK.
CI  - Copyright 2005 S. Karger AG, Basel.
FAU - Sasabe, Eri
AU  - Sasabe E
AD  - Department of Oral Oncology, Kochi Medical School, Kochi University, Kohasu, 
      Oko-cho, Nankoku-city, Japan.
FAU - Tatemoto, Yukihiro
AU  - Tatemoto Y
FAU - Li, Dechao
AU  - Li D
FAU - Yamamoto, Tetsuya
AU  - Yamamoto T
FAU - Osaki, Tokio
AU  - Osaki T
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (BAK1 protein, human)
RN  - 0 (BAX protein, human)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (bcl-X Protein)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Apoptosis
MH  - Calcium/metabolism
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - Cell Line, Tumor
MH  - Cytochromes c/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Membrane Proteins/metabolism
MH  - Mouth Neoplasms/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factors/*metabolism
MH  - Up-Regulation
MH  - bcl-2 Homologous Antagonist-Killer Protein
MH  - bcl-2-Associated X Protein
MH  - bcl-X Protein
EDAT- 2005/08/02 09:00
MHDA- 2005/09/22 09:00
CRDT- 2005/08/02 09:00
PHST- 2005/08/02 09:00 [pubmed]
PHST- 2005/09/22 09:00 [medline]
PHST- 2005/08/02 09:00 [entrez]
AID - CAS065 [pii]
AID - 10.1111/j.1349-7006.2005.00065.x [doi]
PST - ppublish
SO  - Cancer Sci. 2005 Jul;96(7):394-402. doi: 10.1111/j.1349-7006.2005.00065.x.