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

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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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
CYP1B1	Human	lung adenocarcinoma		HEP		protein:increased expression:lung (human)	RGD
FGF9	Human	lung adenocarcinoma		HEP		protein:increased expression:lung (human)	RGD

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
CYP1B1	Human	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	EXP		1,2,3,7,8-Pentachlorodibenzodioxin increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	ISO	RGD:736765	1,2,3,7,8-Pentachlorodibenzodioxin increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	ISO	RGD:736765	1,2,3,7,8-Pentachlorodibenzodioxin increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	EXP		1,2,3,7,8-Pentachlorodibenzodioxin increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Rat	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	ISO	RGD:735806	1,2,3,7,8-Pentachlorodibenzodioxin increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Mouse	1,2,3,7,8-Pentachlorodibenzodioxin	increases expression	ISO	RGD:735806	1,2,3,7,8-Pentachlorodibenzodioxin increases expression of FGF9 mRNA in lung epithelial cell	RGD
CYP1B1	Human	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	EXP		2,3,4,7,8-Pentachlorodibenzofuran increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	ISO	RGD:736765	2,3,4,7,8-Pentachlorodibenzofuran increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	ISO	RGD:736765	2,3,4,7,8-Pentachlorodibenzofuran increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	EXP		2,3,4,7,8-Pentachlorodibenzofuran increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Rat	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	ISO	RGD:735806	2,3,4,7,8-Pentachlorodibenzofuran increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Mouse	2,3,4,7,8-Pentachlorodibenzofuran	increases expression	ISO	RGD:735806	2,3,4,7,8-Pentachlorodibenzofuran increases expression of FGF9 mRNA in lung epithelial cell	RGD
CYP1B1	Human	2,3,7,8-tetrachlorodibenzodioxine	increases expression	EXP		2,3,7,8-tetrachlorodibenzodioxine increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	2,3,7,8-tetrachlorodibenzodioxine	increases expression	ISO	RGD:736765	2,3,7,8-tetrachlorodibenzodioxine increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	2,3,7,8-tetrachlorodibenzodioxine	increases expression	ISO	RGD:736765	2,3,7,8-tetrachlorodibenzodioxine increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	2,3,7,8-tetrachlorodibenzodioxine	increases expression	EXP		2,3,7,8-tetrachlorodibenzodioxine increases expression of FGF9 mRNA and protein in lung epithelial cell	RGD
Fgf9	Rat	2,3,7,8-tetrachlorodibenzodioxine	increases expression	ISO	RGD:735806	2,3,7,8-tetrachlorodibenzodioxine increases expression of FGF9 mRNA and protein in lung epithelial cell	RGD
Fgf9	Mouse	2,3,7,8-tetrachlorodibenzodioxine	increases expression	ISO	RGD:735806	2,3,7,8-tetrachlorodibenzodioxine increases expression of FGF9 mRNA and protein in lung epithelial cell	RGD
CYP1B1	Human	benzo[a]pyrene	increases expression	EXP		benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	benzo[a]pyrene	increases expression	ISO	RGD:736765	benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	benzo[a]pyrene	increases expression	ISO	RGD:736765	benzo[a]pyrene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	benzo[a]pyrene	increases expression	EXP		benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell	RGD
Fgf9	Rat	benzo[a]pyrene	increases expression	ISO	RGD:735806	benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell	RGD
Fgf9	Mouse	benzo[a]pyrene	increases expression	ISO	RGD:735806	benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell	RGD
CYP1B1	Human	Benzo[k]fluoranthene	increases expression	EXP		Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	Benzo[k]fluoranthene	increases expression	ISO	RGD:736765	Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	Benzo[k]fluoranthene	increases expression	ISO	RGD:736765	Benzo[k]fluoranthene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	Benzo[k]fluoranthene	increases expression	EXP		Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cell	RGD
Fgf9	Rat	Benzo[k]fluoranthene	increases expression	ISO	RGD:735806	Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cell	RGD
Fgf9	Mouse	Benzo[k]fluoranthene	increases expression	ISO	RGD:735806	Benzo[k]fluoranthene increases expression of FGF9 mRNA in lung cell	RGD
CYP1B1	Human	dibenz[a,h]anthracene	increases expression	EXP		dibenz[a,h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	dibenz[a,h]anthracene	increases expression	ISO	RGD:736765	dibenz[a,h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	dibenz[a,h]anthracene	increases expression	ISO	RGD:736765	dibenz[a,h]anthracene increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	dibenz[a,h]anthracene	increases expression	EXP		dibenz[a,h]anthracene increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Rat	dibenz[a,h]anthracene	increases expression	ISO	RGD:735806	dibenz[a,h]anthracene increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Mouse	dibenz[a,h]anthracene	increases expression	ISO	RGD:735806	dibenz[a,h]anthracene increases expression of FGF9 mRNA in lung epithelial cell	RGD
FGF9	Human	dimethoxyflavone	multiple interactions	EXP		dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]	RGD
Fgf9	Rat	dimethoxyflavone	multiple interactions	ISO	RGD:735806	dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]	RGD
Fgf9	Mouse	dimethoxyflavone	multiple interactions	ISO	RGD:735806	dimethoxyflavone inhibits the reaction [benzo[a]pyrene increases expression of FGF9 mRNA and protein in lung cell]	RGD
CYP1B1	Human	pentachlorobiphenyl	increases expression	EXP		pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	pentachlorobiphenyl	increases expression	ISO	RGD:736765	pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	pentachlorobiphenyl	increases expression	ISO	RGD:736765	pentachlorobiphenyl increases expression of CYP1B1 mRNA in lung epithelial cell	RGD
FGF9	Human	pentachlorobiphenyl	increases expression	EXP		pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Rat	pentachlorobiphenyl	increases expression	ISO	RGD:735806	pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cell	RGD
Fgf9	Mouse	pentachlorobiphenyl	increases expression	ISO	RGD:735806	pentachlorobiphenyl increases expression of FGF9 mRNA in lung epithelial cell	RGD
CYP1B1	Human	trichlorobiphenyl	decreases expression	EXP		trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Mouse	trichlorobiphenyl	decreases expression	ISO	RGD:736765	trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell	RGD
Cyp1b1	Rat	trichlorobiphenyl	decreases expression	ISO	RGD:736765	trichlorobiphenyl decreases expression of CYP1B1 mRNA in lung epithelial cell	RGD

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)

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