RGD Reference Report - Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas. - Rat Genome Database

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Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas.

Authors: Wang, Chien-Kai  Chang, Han  Chen, Po-Hung  Chang, Jinghua Tsai  Kuo, Yu-Chun  Ko, Jiunn-Liang  Lin, Pinpin 
Citation: Wang CK, etal., Int J Cancer. 2009 Aug 15;125(4):807-15. doi: 10.1002/ijc.24348.
RGD ID: 152177688
Pubmed: PMID:19358281   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.24348   (Journal Full-text)

We had previously reported that aryl hydrocarbon receptors (AhRs) are overexpressed in lung adenocarcinomas. Benzo[a]pyrene (BaP), an AhR agonist, increased FGF-9 expression in human lung adenocarcinoma cells. Similarly, several AhR agonists increased FGF-9 mRNA levels, and BaP-induced FGF-9 expression was prevented by cotreatment with AhR antagonist in human lung adenocarcinoma cells. Furthermore, AhR agonists increased transcriptional activity of FGF-9 promoter. Modulation of AhR expression via RNA interference or transient overexpression respectively reduced or increased both constitutive and BaP-induced FGF-9 expression in human lung cells. These results suggested that AhR activation and overexpression increased FGF-9 expression in lung cells. FGF-9 increased growth of lung fibroblasts but not that of lung adenocarcinoma cells. However, conditioned media collected from FGF-9-treated fibroblasts increased cell growth of lung adenocarcinoma cells. Furthermore, lung adenocarcinoma cells expressed FGF receptor 2 and cotreatment with anti-FGF receptor 2 prevented the interaction between fibroblasts and tumor cells. It is likely that FGF-9-stimulated fibroblasts secreted unknown factors, which activated FGF receptor 2 and subsequently promoted growth of lung adenocarcinoma cells. We further compared AhR and FGF-9 expression in 146 non-small cell lung cancer (NSCLC) cases by immunohistochemistry. FGF-9 expression was more common in adenocarcinomas than in squamous cell carcinomas. Furthermore, FGF-9 and AhR expression were well correlated in lung adenocarcinomas. These results suggest that AhR expression correlated positively with FGF-9 expression in lung adenocarcinomas, which might promote tumor growth by modulating communication between tumor cells and fibroblasts. Preventing AhR overexpression or disturbing FGF-9 function may reduce the development of lung adenocarcinomas. (c) 2009 UICC.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP1B1Humanlung adenocarcinoma  HEP protein:increased expression:lung (human)RGD 
FGF9Humanlung adenocarcinoma  HEP protein:increased expression:lung (human)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP1B1Human1,2,3,7,8-Pentachlorodibenzodioxin increases expression EXP 1 more ...RGD 
Cyp1b1Mouse1,2,3,7,8-Pentachlorodibenzodioxin increases expression ISOCYP1B1 (Homo sapiens)1 more ...RGD 
Cyp1b1Rat1,2,3,7,8-Pentachlorodibenzodioxin increases expression ISOCYP1B1 (Homo sapiens)1 more ...RGD 
FGF9Human1,2,3,7,8-Pentachlorodibenzodioxin increases expression EXP 1 more ...RGD 
Fgf9Rat1,2,3,7,8-Pentachlorodibenzodioxin increases expression ISOFGF9 (Homo sapiens)1 more ...RGD 
Fgf9Mouse1,2,3,7,8-Pentachlorodibenzodioxin increases expression ISOFGF9 (Homo sapiens)1 more ...RGD 
CYP1B1Human2,3,4,7,8-Pentachlorodibenzofuran increases expression EXP 2 more ...RGD 
Cyp1b1Mouse2,3,4,7,8-Pentachlorodibenzofuran increases expression ISOCYP1B1 (Homo sapiens)2 more ...RGD 
Cyp1b1Rat2,3,4,7,8-Pentachlorodibenzofuran increases expression ISOCYP1B1 (Homo sapiens)2 more ...RGD 
FGF9Human2,3,4,7,8-Pentachlorodibenzofuran increases expression EXP 2 more ...RGD 
Fgf9Rat2,3,4,7,8-Pentachlorodibenzofuran increases expression ISOFGF9 (Homo sapiens)2 more ...RGD 
Fgf9Mouse2,3,4,7,8-Pentachlorodibenzofuran increases expression ISOFGF9 (Homo sapiens)2 more ...RGD 
CYP1B1Human2,3,7,8-tetrachlorodibenzodioxine increases expression EXP 2 more ...RGD 
Cyp1b1Rat2,3,7,8-tetrachlorodibenzodioxine increases expression ISOCYP1B1 (Homo sapiens)2 more ...RGD 
Cyp1b1Mouse2,3,7,8-tetrachlorodibenzodioxine increases expression ISOCYP1B1 (Homo sapiens)2 more ...RGD 
FGF9Human2,3,7,8-tetrachlorodibenzodioxine increases expressionEXP 2 more ...RGD 
Fgf9Rat2,3,7,8-tetrachlorodibenzodioxine increases expressionISOFGF9 (Homo sapiens)2 more ...RGD 
Fgf9Mouse2,3,7,8-tetrachlorodibenzodioxine increases expressionISOFGF9 (Homo sapiens)2 more ...RGD 
CYP1B1Humanbenzo[a]pyrene increases expression EXP benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Mousebenzo[a]pyrene increases expression ISOCYP1B1 (Homo sapiens)benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Ratbenzo[a]pyrene increases expression ISOCYP1B1 (Homo sapiens)benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
FGF9Humanbenzo[a]pyrene increases expression EXP benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cellRGD 
Fgf9Ratbenzo[a]pyrene increases expression ISOFGF9 (Homo sapiens)benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cellRGD 
Fgf9Mousebenzo[a]pyrene increases expression ISOFGF9 (Homo sapiens)benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cellRGD 
CYP1B1HumanBenzo[k]fluoranthene increases expression EXP Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1MouseBenzo[k]fluoranthene increases expression ISOCYP1B1 (Homo sapiens)Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1RatBenzo[k]fluoranthene increases expression ISOCYP1B1 (Homo sapiens)Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
FGF9HumanBenzo[k]fluoranthene increases expression EXP Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cellRGD 
Fgf9RatBenzo[k]fluoranthene increases expression ISOFGF9 (Homo sapiens)Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cellRGD 
Fgf9MouseBenzo[k]fluoranthene increases expression ISOFGF9 (Homo sapiens)Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cellRGD 
CYP1B1Humandibenz[a,h]anthracene increases expression EXP dibenz[a and h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Mousedibenz[a,h]anthracene increases expression ISOCYP1B1 (Homo sapiens)dibenz[a and h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Ratdibenz[a,h]anthracene increases expression ISOCYP1B1 (Homo sapiens)dibenz[a and h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
FGF9Humandibenz[a,h]anthracene increases expression EXP dibenz[a and h]anthracene increases expression of FGF9 mRNA in lung epithelial cellRGD 
Fgf9Ratdibenz[a,h]anthracene increases expression ISOFGF9 (Homo sapiens)dibenz[a and h]anthracene increases expression of FGF9 mRNA in lung epithelial cellRGD 
Fgf9Mousedibenz[a,h]anthracene increases expression ISOFGF9 (Homo sapiens)dibenz[a and h]anthracene increases expression of FGF9 mRNA in lung epithelial cellRGD 
FGF9Humandimethoxyflavone multiple interactionsEXP dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]RGD 
Fgf9Ratdimethoxyflavone multiple interactionsISOFGF9 (Homo sapiens)dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]RGD 
Fgf9Mousedimethoxyflavone multiple interactionsISOFGF9 (Homo sapiens)dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]RGD 
CYP1B1Humanpentachlorobiphenyl increases expression EXP pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Mousepentachlorobiphenyl increases expression ISOCYP1B1 (Homo sapiens)pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Ratpentachlorobiphenyl increases expression ISOCYP1B1 (Homo sapiens)pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell RGD 
FGF9Humanpentachlorobiphenyl increases expression EXP pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cellRGD 
Fgf9Ratpentachlorobiphenyl increases expression ISOFGF9 (Homo sapiens)pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cellRGD 
Fgf9Mousepentachlorobiphenyl increases expression ISOFGF9 (Homo sapiens)pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cellRGD 
CYP1B1Humantrichlorobiphenyl decreases expression EXP trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Mousetrichlorobiphenyl decreases expression ISOCYP1B1 (Homo sapiens)trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell RGD 
Cyp1b1Rattrichlorobiphenyl decreases expression ISOCYP1B1 (Homo sapiens)trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp1b1  (cytochrome P450, family 1, subfamily b, polypeptide 1)
Fgf9  (fibroblast growth factor 9)

Genes (Mus musculus)
Cyp1b1  (cytochrome P450, family 1, subfamily b, polypeptide 1)
Fgf9  (fibroblast growth factor 9)

Genes (Homo sapiens)
CYP1B1  (cytochrome P450 family 1 subfamily B member 1)
FGF9  (fibroblast growth factor 9)


Additional Information