PMID- 23625689
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20211021
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 53
IP  - 10
DP  - 2014 Oct
TI  - The Ah receptor regulates growth factor expression in head and neck squamous cell 
      carcinoma cell lines.
PG  - 765-76
LID - 10.1002/mc.22032 [doi]
AB  - Previous studies in head and neck squamous cell carcinoma (HNSCC) cell lines have 
      revealed that the Ah receptor (AHR) plays a significant role in mediating the 
      "aggressive" phenotype of these cells, which includes enhanced inflammatory 
      signaling (e.g., IL6) and migratory potential. Here we sought to identify 
      putative novel targets of the AHR associated with enhanced tumor invasiveness. 
      Global gene expression analysis identified a number of genes that are repressed 
      upon treatment of OSC-19 or HN30 cells with an AHR antagonist. Three growth 
      factors were targets of AHR activity; amphiregulin (AREG), epiregulin (EREG), and 
      platelet-derived growth factor A (PDGFA) were repressed by an AHR antagonist and 
      further examined. Quantitative PCR analysis, ELISA, and siRNA-mediated knock down 
      of AHR revealed an attenuation of basal and/or induced levels of expression of 
      these growth factors in two HNSCC lines, following AHR antagonism. In silico 
      analysis revealed that these growth factors possess dioxin-like response 
      elements. Two other AHR ligands, 6-formylindolo[3,2-b]carbazole and 
      benzo(a)pyrene (BP) also elicited similar responses. In conclusion, this study 
      identified AREG, EREG, and PDGFA as growth factor targets of AHR activity 
      associated with metastatic phenotype of HNSCC cells, suggesting that attenuation 
      of AHR activity may be a therapeutic strategy.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - John, Kaarthik
AU  - John K
AD  - Center for Molecular Toxicology and Carcinogenesis and the Department of 
      Veterinary and Biomedical Sciences, The Pennsylvania State University, University 
      Park, Pennsylvania; DuPont Haskell Global Centers for Health and Environmental 
      Sciences, Newark, Delaware.
FAU - Lahoti, Tejas S
AU  - Lahoti TS
FAU - Wagner, Kelly
AU  - Wagner K
FAU - Hughes, Jarod M
AU  - Hughes JM
FAU - Perdew, Gary H
AU  - Perdew GH
LA  - eng
GR  - R01 ES004869/ES/NIEHS NIH HHS/United States
GR  - R01 ES019964/ES/NIEHS NIH HHS/United States
GR  - ES004869/ES/NIEHS NIH HHS/United States
GR  - ES019964/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130427
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide)
RN  - 0 (Azo Compounds)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (platelet-derived growth factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Azo Compounds/pharmacology
MH  - Carcinoma, Squamous Cell
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Epidermal Growth Factor/*genetics/metabolism
MH  - Epiregulin
MH  - Fibroblast Growth Factor 2/*genetics/metabolism
MH  - Gene Expression
MH  - *Gene Expression Regulation, Neoplastic
MH  - Head and Neck Neoplasms
MH  - Humans
MH  - Platelet-Derived Growth Factor/*genetics/metabolism
MH  - Pyrazoles/pharmacology
MH  - Receptors, Aryl Hydrocarbon/antagonists & inhibitors/*physiology
MH  - Squamous Cell Carcinoma of Head and Neck
PMC - PMC4388041
MID - NIHMS676496
OTO - NOTNLM
OT  - AHR
OT  - antagonist
OT  - aryl hydrocarbon receptor
OT  - dioxin
OT  - growth factors
OT  - head and neck cancer
EDAT- 2013/04/30 06:00
MHDA- 2014/11/05 06:00
PMCR- 2015/04/07
CRDT- 2013/04/30 06:00
PHST- 2012/11/30 00:00 [received]
PHST- 2013/03/11 00:00 [revised]
PHST- 2013/03/12 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
PHST- 2015/04/07 00:00 [pmc-release]
AID - 10.1002/mc.22032 [doi]
PST - ppublish
SO  - Mol Carcinog. 2014 Oct;53(10):765-76. doi: 10.1002/mc.22032. Epub 2013 Apr 27.