Up-regulation of osteopontin expression by aryl hydrocarbon receptor via both ligand-dependent and ligand-independent pathways in lung cancer

Chuang, Chun‐Yi; Chang, Han; Lin, Pinpin; Sun, Shih-Jung; Chen, Po-Hung; Lin, Ying‐Chu; Sheu, Gwo‐Tarng; Ko, Jiunn‐Liang; Hsu, Shih-Lan; Chang, Jinghua Tsai

doi:10.1016/j.gene.2011.10.019

Cited by 29 publications

(31 citation statements)

References 44 publications

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“…6B) showed that Western diet caused an increase in Cyp1b1 mRNA levels, and in turn, that Western diet containing NF or CH-223191 caused a reduction of Cyp1b1 mRNA to approach control levels. Furthermore, mRNA expression levels in liver of other AHR-regulated genes involved in obesity were decreased by AHR inhibition, including the Foxo1 [39], Scd1 [40–42], and Spp1 [43] genes. The results are consistent with a hypothesis that the AHR antagonists work by inhibiting the transcriptional activity of the AHR to reduce the expression of genes required for obesity, e.g., Cyp1b1 .…”

Section: Resultsmentioning

confidence: 99%

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Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice

et al. 2017

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Inhibition of the aryl hydrocarbon receptor (AHR) prevents Western diet-induced obesity and fatty liver in C57Bl/6J (B6) male mice. The AHR is a ligand-activated nuclear receptor that regulates genes involved in xenobiotic metabolism and T cell differentiation. Here, we tested the hypothesis that AHR antagonism would also prevent obesity and fatty liver in female mice and that B6 mice (higher-affinity AHR) and congenic B6.D2 mice (lower-affinity AHR) would differentially respond to AHR inhibition. Female and male adult B6 and B6.D2 mice were fed control and Western diets with and without α-naphthoflavone, an AHR inhibitor. A nonlinear mixed model analysis was developed to project asymptote body mass. We found that obesity, adiposity, and liver steatosis were reduced to near control levels in all female and male B6 and B6.D2 experimental groups fed Western diet with α-naphthoflavone. However, differences were noted in that female B6.D2 versus B6 mice on Western diet became more obese; and in general, female mice to that of male mice had a greater fat mass to body mass ratio, were less responsive to α-naphthoflavone, and had reduced liver steatosis and hepatomegaly. We report that male mice fed Western diet containing α-naphthoflavone or CH-223191, another AHR inhibitor, caused reduced mRNA levels of several liver genes involved in metabolism, including Cyp1b1 and Scd1, offering evidence for a possible mechanism by which the AHR regulates obesity. In conclusion, although there are some sex- and Ahr allelic-dependent differences, AHR inhibition prevents obesity and liver steatosis in both males and females regardless of the ligand-binding capacity of the AHR. We also present evidence consistent with the notion that an AHR-CYP1B1-SCD1 axis is involved in obesity providing potentially convenient and effective targets for treatment.

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Section: Resultsmentioning

confidence: 99%

“…SPP1 (osteopontin) is a sensitive marker for obesity in mice and humans [53–55]. Loss of the Spp1 gene causes obesity resistance in mice fed a high-fat diet [56] and is a gene regulated by the AHR [43]. The whole-body deletion of the canonical AHR-regulated Cyp1b1 gene prevents obesity in mice fed a high-fat diet [24, 25].…”

Section: Discussionmentioning

confidence: 99%

Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice

et al. 2017

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“…The AhR pathway is vital for tissue repair, including inflammation, angiogenesis, and ECM remodeling [16]. Recent studies have shown that AhR was associated with the remodeling process in many tissues, such as the gut [17], dermal fibroblasts [18], and lung cancer [19]. However, the role of AhR in tissue remodeling of CRS is unknown.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis

Chen

Xiao²,

Liu³

et al. 2017

ORL

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Objective: This study aimed to determine the aryl hydrocarbon receptor (AhR) and transforming growth factor beta 1 (TGF-β1) expression levels in chronic rhinosinusitis (CRS) and their possible correlation with allergic state and tissue remodeling. Methods: Patients were enrolled and divided into the following groups: CRS without nasal polyps (NP) without allergic rhinitis (AR) (CRSsNPsAR; n = 20), CRS with NP with AR (CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of AhR and TGF-β1 were analyzed by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting. Results: The collagen amounts as well as AhR and TGF-β1 mRNA and protein expression levels were significantly increased in the CRSsNPsAR group compared with the CRSwNP (CRSwNPsAR and CRSwNPwAR) samples (p < 0.01). However, higher collagen amounts (p < 0.05) and higher TGF-β1 (p < 0.05) but lower AhR expression levels (p < 0.05) were detected in the CRSwNPwAR versus the CRSwNPsAR patients. Both AhR and TGF-β1 expression were positively correlated with the collagen level in CRS samples (p < 0.01). Conclusions: Elevated AhR expression may be involved in the progression of tissue remodeling in CRSsNPsAR similar to TGF-β1 expression. Conversely, lower AhR expression may be involved in allergic reactions in CRSwNPwAR.

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“…We have observed that 65% of NSCLC specimens express high levels of OPN protein [25]. The predominant form of OPN expressed in lung cancer cell lines and lung tumors is OPN-a.…”

Section: Introductionmentioning

confidence: 99%

Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

Sun

Sheu

et al. 2016

Oncotarget

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Osteopontin (OPN), a phosphorylated glycoprotein, is frequently overexpressed in cancer. Among the three OPN isoforms, OPN-a is the most highly expressed in lung cancer cell lines and lung tumors. Overexpression of OPN-a greatly reduced CL1-5 lung adenocarcinoma cell growth, but had no effect on growth in A549 lung adenocarcinoma cells. Examination of the expression of integrins and CD44, which are possible OPN-a receptors, revealed that differences in integrin β3 levels might explain this discrepancy between CL1-5 and A549 cells. When integrin β3 was ectopically expressed in A549 cells, OPN-a inhibited their growth, whereas OPN-a increased cell growth following integrin β3 knockdown in CL1-5 cells. This OPN-a-induced increase in growth appeared to result from activation of the CD44/NFκB pathway. Our results demonstrated that OPN-a inhibits growth of cells with high integrin β3 levels and increases growth via activation of the CD44/NFκB pathway in cells with low integrin β3 levels. Thus, OPN-a, integrin β3, and CD44 interact to affect lung cancer cell growth, and this study may aid in the development of cancer treatment strategies involving these molecules.

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Up-regulation of osteopontin expression by aryl hydrocarbon receptor via both ligand-dependent and ligand-independent pathways in lung cancer

Cited by 29 publications

References 44 publications

Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice

Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice

Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis

Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

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