PMID- 17651772
OWN - NLM
STAT- MEDLINE
DCOM- 20071128
LR  - 20211203
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 224
IP  - 2
DP  - 2007 Oct 15
TI  - MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose 
      causing a significant incidence of renal carcinoma.
PG  - 174-81
AB  - Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA 
      over 7 days, 21 days and 12 months were analysed for various cell signalling 
      proteins known to be potentially involved in chemical carcinogenicity. OTA was 
      found to increase the phosphorylation of atypical-PKC. This was correlated with a 
      selective downstream activation of the MAP-kinase extracellular regulated kinases 
      isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, 
      analysis of effectors acting upstream of PKC indicated a possible mobilisation of 
      the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent 
      kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic 
      activity associated with enhanced HDAC3 protein expression was also observed. 
      These findings are potentially relevant with respect to the understanding of OTA 
      nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to 
      play a role in tumour development. Furthermore, PKC and the MEK-ERK MAP-kinase 
      pathways are known to play important roles in cell proliferation, cell survival, 
      anti-apoptotic activity and renal cancer development.
FAU - Marin-Kuan, M
AU  - Marin-Kuan M
AD  - Nestle Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, 
      Switzerland. maricel.marin-kuan@rdls.nestle.com
FAU - Nestler, S
AU  - Nestler S
FAU - Verguet, C
AU  - Verguet C
FAU - Bezencon, C
AU  - Bezencon C
FAU - Piguet, D
AU  - Piguet D
FAU - Delatour, T
AU  - Delatour T
FAU - Mantle, P
AU  - Mantle P
FAU - Cavin, C
AU  - Cavin C
FAU - Schilter, B
AU  - Schilter B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070703
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Carcinogens)
RN  - 0 (Elk1 protein, rat)
RN  - 0 (Ochratoxins)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - 1779SX6LUY (ochratoxin A)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (Pdpk1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - EC 3.5.1.98 (histone deacetylase 3)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Animals
MH  - Blotting, Western
MH  - Carcinogens/administration & dosage/*toxicity
MH  - Gene Expression Regulation/drug effects
MH  - Histone Deacetylases/metabolism
MH  - Kidney/metabolism
MH  - Kidney Neoplasms/chemically induced/physiopathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/*drug effects/metabolism
MH  - Mitogen-Activated Protein Kinase 3/*drug effects/metabolism
MH  - Ochratoxins/administration & dosage/*toxicity
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptor, IGF Type 1/drug effects/metabolism
MH  - Ribosomal Protein S6 Kinases, 90-kDa/drug effects/metabolism
MH  - Time Factors
MH  - ets-Domain Protein Elk-1/drug effects/metabolism
EDAT- 2007/07/27 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/07/27 09:00
PHST- 2006/11/21 00:00 [received]
PHST- 2007/05/16 00:00 [revised]
PHST- 2007/06/26 00:00 [accepted]
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - S0041-008X(07)00286-4 [pii]
AID - 10.1016/j.taap.2007.06.014 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2007 Oct 15;224(2):174-81. doi: 
      10.1016/j.taap.2007.06.014. Epub 2007 Jul 3.