PMID- 15385644
OWN - NLM
STAT- MEDLINE
DCOM- 20041126
LR  - 20161124
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 66
IP  - 4
DP  - 2004 Oct
TI  - Superinduction of CYP1A1 in MCF10A cultures by cycloheximide, anisomycin, and 
      puromycin: a process independent of effects on protein translation and unrelated 
      to suppression of aryl hydrocarbon receptor proteolysis by the proteasome.
PG  - 936-47
AB  - Exposure of the human breast epithelial cell line MCF10A to > or = 1 microg/ml 
      cycloheximide (CHX)-induced accumulations of CYP1A1 mRNA 6-fold greater than that 
      achieved with only 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cotreatment with 
      CHX and TCDD caused superinduction of CYP1A1 with accumulations of CYP1A1 mRNA 
      30-fold greater than that achieved with only TCDD. Similar results were obtained 
      with the protein translation inhibitors anisomycin (ANS) and puromycin (PUR). 
      Intra- and interinhibitor comparisons of dose/concentration response curves 
      demonstrated the absence of a quantitative relationship between [3H]leucine 
      incorporation and CYP1A1 induction/superinduction. The inducing/superinducing 
      activities of CHX were suppressed by coincubation with the aryl hydrocarbon 
      receptor (AhR) antagonists alpha-naphthoflavone and 3'-methoxy-4'-nitroflavone 
      (PD168641). Electrophoretic mobility shift assays demonstrated that nuclear 
      extracts from CHX-treated and CHX + TCDD cotreated cultures formed approximately 
      58 and approximately 340% of the AhR/DNA complexes obtained with TCDD-treated 
      cultures, respectively. In contrast, rat liver extracts did not form AhR/DNA 
      complexes after in vitro transformation with CHX. AhR turnover in TCDD-treated 
      hepatoma 1c1c7 cultures was suppressed by cotreatment with CHX. In contrast, CHX 
      or ANS treatment of MCF10A cultures induced AhR loss and enhanced AhR loss in 
      cultures cotreated with TCDD. Cotreatment with 
      N-benzoyloxycarbonyl-(Z)-Leu-Leu-leucinal (MG132) but not leptomycin B suppressed 
      AhR loss. Hence, in MCF10A cells, CHX is not an AhR agonist but can superinduce 
      CYP1A1 via an AhR-dependent mechanism; CYP1A1 superinduction by translation 
      inhibitors is neither quantitatively related to effects on protein synthesis nor 
      due to a generalized prevention of AhR proteolysis, and proteasome-mediated 
      degradation of the activated AhR can occur in the nucleus.
FAU - Joiakim, Aby
AU  - Joiakim A
AD  - Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 
      48201, USA.
FAU - Mathieu, Patricia A
AU  - Mathieu PA
FAU - Elliott, Althea A
AU  - Elliott AA
FAU - Reiners, John J Jr
AU  - Reiners JJ Jr
LA  - eng
GR  - ES009392/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Leupeptins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 10028-17-8 (Tritium)
RN  - 4A6ZS6Q2CL (Puromycin)
RN  - 6C74YM2NGI (Anisomycin)
RN  - 9007-49-2 (DNA)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - GMW67QNF9C (Leucine)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN  - Y031I2N1EO (leptomycin B)
SB  - IM
MH  - Anisomycin/*pharmacology
MH  - Cycloheximide/*pharmacology
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Cytochrome P-450 CYP1A2/biosynthesis
MH  - DNA/drug effects/metabolism
MH  - Enzyme Induction/drug effects
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Humans
MH  - Leucine/metabolism
MH  - Leupeptins/pharmacology
MH  - Polychlorinated Dibenzodioxins/pharmacology
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Biosynthesis/drug effects
MH  - Puromycin/*pharmacology
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Tritium
MH  - Tumor Cells, Cultured
EDAT- 2004/09/24 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - 66/4/936 [pii]
AID - 10.1124/mol.66.4. [doi]
PST - ppublish
SO  - Mol Pharmacol. 2004 Oct;66(4):936-47. doi: 10.1124/mol.66.4..