PMID- 12020348
OWN - NLM
STAT- MEDLINE
DCOM- 20021008
LR  - 20211203
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 366
IP  - Pt 1
DP  - 2002 Aug 15
TI  - Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma 
      cells: involvement of nuclear factor-kappaB, stimulatory protein-1 transcription 
      factors and mitogen-activated protein kinase pathways.
PG  - 299-306
AB  - Monocyte chemoattractant protein-1 (MCP-1) expression is found in malignant 
      melanoma and melanoma metastases. Since areas of hypoxia/reoxygenation (H/R) are 
      a common feature of malignant tumours and metastases, we addressed the question 
      whether melanoma cells produce MCP-1 upon exposure to H/R. In the present study, 
      we show that melanoma cells up-regulate MCP-1 mRNA and protein under H/R. By 
      means of reporter gene analysis, we further demonstrate that H/R induces 
      transcriptional activation of the MCP-1 promoter carrying a stimulatory protein-1 
      (SP1) and two nuclear factor-kappaB (NF-kappaB) binding motifs. Accordingly, 
      H/R-stimulated melanoma cells showed enhanced binding activity of both 
      transcription factors NF-kappaB and SP1 in electrophoretic mobility-shift assay. 
      A common upstream activator of NF-kappaB, inhibitory kappaBalpha kinase, was not 
      significantly activated under H/R conditions. Further analysis of upstream 
      signalling events revealed that members of the mitogen-activated protein kinases 
      family, namely extracellular signal-regulated protein kinase, c-Jun N-terminal 
      kinase/ stress-activated protein kinase and p38 stress kinase, may be involved in 
      MCP-1 transcriptional regulation under H/R. In summary, we conclude that H/R 
      induces MCP-1 production in melanoma cells via the co-operative action of both 
      transcription factors NF-kappaB and SP1, and involves mitogen-activated protein 
      kinase signalling pathways. Functionally, H/R-induced MCP-1 production may 
      contribute to tumour progression by committing selective pressure on tumour cells 
      via chemoattraction and activation of tumour-infiltrating monocytes/macrophages.
FAU - Kunz, Manfred
AU  - Kunz M
AD  - Department of Dermatology, University of Rostock, Augustenstr. 80-84, 18055 
      Rostock, Germany. manfred.kunz@med.uni-rostock.de
FAU - Bloss, Gisela
AU  - Bloss G
FAU - Gillitzer, Reinhard
AU  - Gillitzer R
FAU - Gross, Gerd
AU  - Gross G
FAU - Goebeler, Matthias
AU  - Goebeler M
FAU - Rapp, Ulf R
AU  - Rapp UR
FAU - Ludwig, Stephan
AU  - Ludwig S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA, Complementary)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Organic Chemicals)
RN  - 0 (PD 98058)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Blotting, Northern
MH  - Cell Nucleus/metabolism
MH  - Chemokine CCL2/*genetics/*metabolism
MH  - DNA, Complementary/metabolism
MH  - Disease Progression
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - *Hypoxia/metabolism
MH  - I-kappa B Kinase
MH  - Immunoblotting
MH  - Luciferases/metabolism
MH  - *MAP Kinase Signaling System
MH  - Melanoma/*metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/*metabolism
MH  - *Organic Chemicals
MH  - Oxygen/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC1222766
EDAT- 2002/05/22 10:00
MHDA- 2002/10/09 04:00
PMCR- 2003/02/15
CRDT- 2002/05/22 10:00
PHST- 2002/05/21 00:00 [accepted]
PHST- 2002/04/26 00:00 [revised]
PHST- 2001/11/30 00:00 [received]
PHST- 2002/05/22 10:00 [pubmed]
PHST- 2002/10/09 04:00 [medline]
PHST- 2002/05/22 10:00 [entrez]
PHST- 2003/02/15 00:00 [pmc-release]
AID - BJ20011749 [pii]
AID - 10.1042/BJ20011749 [doi]
PST - ppublish
SO  - Biochem J. 2002 Aug 15;366(Pt 1):299-306. doi: 10.1042/BJ20011749.