PMID- 16929009
OWN - NLM
STAT- MEDLINE
DCOM- 20070313
LR  - 20190107
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 94
IP  - 1
DP  - 2006 Nov
TI  - In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces amphiregulin 
      gene expression in the developing mouse ureter.
PG  - 163-74
AB  - Exposure to the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin 
      (TCDD), produces hydronephrosis in developing mice, the etiology of which 
      involves hyperplasia within the ureteric luminal epithelium. Dysregulation of 
      epidermal growth factor receptor (EGFR), EGF, and transforming growth 
      factor-alpha expression has been implicated as playing a role in TCDD-induced 
      hydronephrosis. In this study, changes in the expression of genes encoding the 
      EGFR and its cognate ligands in response to TCDD were evaluated within the 
      developing ureter. C57BL/6 dams were injected ip with 30 mug/kg TCDD on 
      gestational day (GD) 13 or 16 and fetal tissues removed on GD 17. Aryl 
      hydrocarbon receptor (AHR) and AHR nuclear translocator messenger RNA (mRNA) were 
      expressed in control and treated fetal tissues at GD 14 and 17. Prototypical AHR 
      target genes, Cyp1a1, Cyp1a2, and Cyp1b1 were upregulated in TCDD-exposed fetal 
      tissues, demonstrating AHR transcriptional activity at these developmental 
      stages. Amphiregulin (AREG) and epiregulin, ligands for the EGFR, were induced at 
      the transcriptional level in ureters of fetuses exposed to TCDD for 24 h. AREG 
      mRNA was also induced by TCDD dose- and time-dependently in the mouse hepatoma 
      cell line Hepa-1c1c7 (Hepa-1), mimicking the induction patterns of CYP1A1 mRNA. 
      Other AHR ligands also induced AREG mRNA in Hepa-1 cells. Furthermore, variant 
      Hepa-1 cells (TAOBP(r)c1 cells) virtually deficient in the AHR failed to display 
      an increase in AREG mRNA in response to TCDD. Taken together, these data suggest 
      that the AHR cross talks with the EGFR signaling pathway by directly inducing the 
      expression of growth factors that are important for EGFR signaling in the 
      developing mouse ureter.
FAU - Choi, Sharon S H
AU  - Choi SS
AD  - Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, 
      Canada.
FAU - Miller, Margaret A
AU  - Miller MA
FAU - Harper, Patricia A
AU  - Harper PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060823
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Benz(a)Anthracenes)
RN  - 0 (Benzofurans)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Teratogens)
RN  - 2NE6H0QPCH (1,2,3,7,8-pentachlorodibenzo-p-dioxin)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - C5PLF6152K (benz(a)anthracene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - G7ED7OIQ5M (1,2,3,4-tetrachlorodibenzofuran)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Benz(a)Anthracenes/administration & dosage/toxicity
MH  - Benzo(a)pyrene/administration & dosage/toxicity
MH  - Benzofurans/administration & dosage/toxicity
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - Dose-Response Relationship, Drug
MH  - EGF Family of Proteins
MH  - Female
MH  - Gene Expression Regulation, Developmental/*drug effects/genetics
MH  - Gestational Age
MH  - Glycoproteins/*genetics
MH  - Injections, Intraperitoneal
MH  - Intercellular Signaling Peptides and Proteins/*genetics
MH  - Male
MH  - Maternal Exposure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polychlorinated Dibenzodioxins/administration & dosage/analogs & 
      derivatives/*toxicity
MH  - Pregnancy
MH  - RNA, Messenger/genetics/isolation & purification/metabolism
MH  - Receptors, Aryl Hydrocarbon/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Teratogens/toxicity
MH  - Ureter/*drug effects/embryology/metabolism
EDAT- 2006/08/25 09:00
MHDA- 2007/03/14 09:00
CRDT- 2006/08/25 09:00
PHST- 2006/08/25 09:00 [pubmed]
PHST- 2007/03/14 09:00 [medline]
PHST- 2006/08/25 09:00 [entrez]
AID - kfl090 [pii]
AID - 10.1093/toxsci/kfl090 [doi]
PST - ppublish
SO  - Toxicol Sci. 2006 Nov;94(1):163-74. doi: 10.1093/toxsci/kfl090. Epub 2006 Aug 23.