PMID- 12651620
OWN - NLM
STAT- MEDLINE
DCOM- 20030612
LR  - 20190607
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 162
IP  - 4
DP  - 2003 Apr
TI  - Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of 
      pancreatic cancer cells through the suppression of glucose metabolism.
PG  - 1283-91
AB  - In the tumor cells exposed to hypoxia, hypoxia-inducible factor-1 
      (HIF-1)-mediated adaptation responses such as angiogenesis and anaerobic 
      metabolism are induced for their survival. We have recently reported that the 
      constitutive expression of HIF-1 alpha renders pancreatic cancer cells resistant 
      to apoptosis induced by hypoxia and glucose deprivation. We then established 
      dominant-negative HIF-1 alpha (dnHIF-1 alpha) transfectants and examined their 
      susceptibility to apoptosis and growth inhibition induced by hypoxia and glucose 
      deprivation in vitro and their tumorigenicity in SCID mice. We further examined 
      the expressions of aldolase A and Glut-1 in vitro and Glut-1 expression and 
      glucose uptake in the tumor tissues and microvessel counts in the tumor tissues. 
      As a result, dnHIF-1 alpha rendered the pancreatic cancer cells sensitive to 
      apoptosis and growth inhibition induced by hypoxia and glucose deprivation. Also 
      it abrogated the enhanced expression of Glut-1 and aldolase A mRNAs under hypoxia 
      and reduced the expression of Glut-1 and the glucose uptake in the tumor tissues 
      and consequently in vivo tumorigenicity. We found no significant difference in 
      the microvessel counts among the tumor tissues. From these results, we suggest 
      that the disruption of the HIF-1 pathway might be effective in the treatment of 
      pancreatic cancers.
FAU - Chen, Jian
AU  - Chen J
AD  - Division of Cancer Pathobiology, Institute for Genetic Medicine, Hokkaido 
      University, and Department of Surgical Oncology, Hokkaido University Graduate 
      School of Medicine, Sapporo, Japan.
FAU - Zhao, Songji
AU  - Zhao S
FAU - Nakada, Kunihiro
AU  - Nakada K
FAU - Kuge, Yuji
AU  - Kuge Y
FAU - Tamaki, Nagara
AU  - Tamaki N
FAU - Okada, Futoshi
AU  - Okada F
FAU - Wang, Jingxin
AU  - Wang J
FAU - Shindo, Masanobu
AU  - Shindo M
FAU - Higashino, Fumihiro
AU  - Higashino F
FAU - Takeda, Kohji
AU  - Takeda K
FAU - Asaka, Masahiro
AU  - Asaka M
FAU - Katoh, Hiroyuki
AU  - Katoh H
FAU - Sugiyama, Toshio
AU  - Sugiyama T
FAU - Hosokawa, Masuo
AU  - Hosokawa M
FAU - Kobayashi, Masanobu
AU  - Kobayashi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenocarcinoma/genetics/metabolism/pathology/prevention & control
MH  - Animals
MH  - Apoptosis
MH  - Biological Transport
MH  - Blotting, Northern
MH  - Cell Division
MH  - Deoxyglucose/pharmacokinetics
MH  - Flow Cytometry
MH  - Genes, Dominant
MH  - Glucose/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kinetics
MH  - Mice
MH  - Mice, SCID
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology/prevention & control
MH  - Recombinant Proteins/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/*genetics/metabolism
MH  - Transfection
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
PMC - PMC1851236
EDAT- 2003/03/26 04:00
MHDA- 2003/06/13 05:00
PMCR- 2003/10/01
CRDT- 2003/03/26 04:00
PHST- 2003/03/26 04:00 [pubmed]
PHST- 2003/06/13 05:00 [medline]
PHST- 2003/03/26 04:00 [entrez]
PHST- 2003/10/01 00:00 [pmc-release]
AID - S0002-9440(10)63924-7 [pii]
AID - 3568 [pii]
AID - 10.1016/s0002-9440(10)63924-7 [doi]
PST - ppublish
SO  - Am J Pathol. 2003 Apr;162(4):1283-91. doi: 10.1016/s0002-9440(10)63924-7.