PMID- 12841876
OWN - NLM
STAT- MEDLINE
DCOM- 20040106
LR  - 20190513
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 94
IP  - 7
DP  - 2003 Jul
TI  - Screening of stress enhancer based on analysis of gene expression profiles: 
      enhancement of hyperthermia-induced tumor necrosis by an MMP-3 inhibitor.
PG  - 644-9
AB  - To improve the therapeutic benefit of hyperthermia, we examined changes of global 
      gene expression after heat shock using DNA microarrays consisting of 12 814 
      clones. HeLa cells were treated for 1 h at 44 degrees C and RNA was extracted 
      from the cells 0, 3, 6, and 12 h after heat shock. The 664 genes that were up or 
      down-regulated after heat shock were classified into 7 clusters using fuzzy 
      adaptive resonance theory (fuzzy ART). There were 41 genes in two clusters that 
      were induced in the early phase after heat shock. In addition to shock response 
      genes, such as hsp70 and hsp40, the stress response genes c-jun, c-fos and egr-1 
      were expressed in the early phase after heat shock. We also found that expression 
      of matrix metalloproteinase 3 (MMP-3) was enhanced during the early response. We 
      therefore investigated the role of MMP-3 in the heat shock response by examining 
      HeLa cell survival after heat treatment in the presence and absence of an MMP-3 
      inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycylhydroxamic acid (NNGH) or 
      N-hydroxy-2(R)-[[4- methoxysulfonyl](3-picolyl)amino]-3-methylbutaneamide 
      hydrochloride (MMI270). The number of surviving cells 3 days after heat treatment 
      significantly decreased, reaching 3.5% for NNGH and 0.2% for MMI270. These 
      results indicate that the MMP-3 inhibitors enhanced heat shock-induced cell death 
      and behaved as stress enhancers in cancer cells. This valuable conclusion was 
      reached as a direct result of the gene expression profiling that was performed in 
      these studies.
FAU - Kato, Naoki
AU  - Kato N
AD  - Department of Biotechnology, School of Engineering, Nagoya University, 
      Chikusa-ku, Nagoya 464-8603, Japan.
FAU - Kobayashi, Takeshi
AU  - Kobayashi T
FAU - Honda, Hiroyuki
AU  - Honda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cell Survival/drug effects
MH  - DNA-Binding Proteins/genetics
MH  - Early Growth Response Protein 1
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, fos
MH  - Genes, jun
MH  - HeLa Cells
MH  - *Hot Temperature
MH  - Humans
MH  - *Immediate-Early Proteins
MH  - Kinetics
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Multigene Family/drug effects
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Protease Inhibitors/*pharmacology
MH  - Transcription Factors/genetics
EDAT- 2003/07/05 05:00
MHDA- 2004/01/07 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2004/01/07 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - 10.1111/j.1349-7006.2003.tb01497.x [doi]
PST - ppublish
SO  - Cancer Sci. 2003 Jul;94(7):644-9. doi: 10.1111/j.1349-7006.2003.tb01497.x.