Preferential Induction of CYP1A1 and CYP1B1 in CCSP-Positive Cells

Chang, Han; Chang, Louis W.; Cheng, Ya-Hsin; Tsai, Wen-Tin; Tsai, Ming-Xian; Lin, Pinpin

doi:10.1093/toxsci/kfj025

Cited by 33 publications

(23 citation statements)

References 49 publications

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“…Along with their secretory properties, they have been implicated in many diverse roles, ranging from a progenitor cell to a detoxifier. Of particular interest to our study, Clara cells have been identified as being the most sensitive in responding to AhR stimuli (32). In our cellular studies described above, after CYP1A1, mucin 5AC was our most consistently expressed gene after AhR activation in the NCI-H441 cell line.…”

Section: Discussionmentioning

confidence: 78%

Arylhydrocarbon Receptor Activation in NCI-H441 Cells and C57BL/6 Mice

Wong

Vogel²,

Kokosinski³

et al. 2010

Am J Respir Cell Mol Biol

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The arylhydrocarbon receptor (AhR) is known for its ability to bind aromatic-containing compounds, which starts a molecular cascade involving the induction of cytochrome P450s and inflammatory cytokines. Our hypothesis is that many inhaled environmental toxicant components activate these inflammatory pathways via an initial binding to the AhR. To test this possibility, we treated Clara cell-derived NCI-H441 cells with the AhR agonist, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), and demonstrated that AhR activation increased the expression of both cytochrome P450 s and inflammatory markers. We also found increased mucin 5AC production with TCDD treatment. Similar results were observed in NCI-H441 cells treated with urban dust particles. Mucin 5AC expression was highly correlated with increased-expression cyclooxygenase-2 and IL-1b, thus implicating these two inflammatory markers as possible conduits for AhR-mediated mucin production. We hypothesize that this increase in mucin 5AC production is a result of inflammation-induced differentiation of our epithelial cell to a mucin-producing cell. This theory is supported by morphological changes observed in the cells, as well as decreased expression of Clara cell secretory protein (CC10). In an in vivo C57BL/6 mouse model, TCDD increased expression of inflammatory cytokines, mucin 5AC, and a number of matrix metalloproteases in whole-lung samples. These changes were not seen in mice in which AhR signaling was repressed. These markers from the whole-lung samples have been correlated to onset of bronchitis, asthma, small airways disease, and fibrosis, and their increased expression further implicates AhR activation in producing the molecular environment for the development of lung injury to occur.

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Section: Discussionmentioning

confidence: 78%

Arylhydrocarbon Receptor Activation in NCI-H441 Cells and C57BL/6 Mice

Wong

Vogel²,

Kokosinski³

et al. 2010

Am J Respir Cell Mol Biol

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“…Western immunoblotting. Cytosolic homogenates were prepared for AhR Western immunoblotting and microsomes were prepared for CYP1B1 Western immunoblotting as previously described (15,23). The samples were separated by 10% SDS-PAGE.…”

Section: àDctmentioning

confidence: 99%

Requirement of Aryl Hydrocarbon Receptor Overexpression for CYP1B1 Up-Regulation and Cell Growth in Human Lung Adenocarcinomas

Chang

Chen

et al. 2007

Clinical Cancer Research

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100

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Purpose: CYP1B1and CYP1A1expression is up-regulated by activation of the aryl hydrocarbon receptor (AhR) through binding of ligands such as cigarette smoke components. We examined the association between AhR, CYP1B1, and CYP1A1expression in noninvasive bronchioloalveolar carcinomas (BAC) and lung adenocarcinomas and investigated the effects of AhR overexpression on cell physiology. Experimental Design: AhR, CYP1B1, and CYP1A1 expression was examined in 107 lung adenocarcinomas and 57 BAC by immunohistochemistry. AhR expression in lung adenocarcinoma H1355 cells was stably reduced by RNA interference (RNAi). AhR, CYP1B1, and CYP1A1 expression was examined using real-time reverse transcription-PCR. Cell physiology was evaluated by measuring anchorage-independent growth and intracellular reactive oxygen species. Results: Expression of AhR and CYP1A1 was associated in smoking adenocarcinoma patients, whereas expression of AhR and CYP1B1was associated regardless of smoking status. The level of CYP1B1, but not CYP1A1, was positively associated with AhR overexpression in BAC. 2,3,7,8-Tetrachlorobenzo-p-dioxin^induced CYP1A1/1B1 expression was reduced in AhR RNAi clones. In the absence of 2,3,7,8-tetrachlorobenzo-p-dioxin, CYP1B1 mRNA levels were reduced in AhR RNAi clones, whereas CYP1A1 mRNA levels were barely detectable. Furthermore, anchorageindependent growth and intracellular oxidative stress were significantly reduced in AhR RNAi cells. Conclusions: In the absence of exogenous AhR ligands (such as cigarette smoke components), AhR overexpression up-regulated the expression of CYP1B1in the early stage of lung adenocarcinoma. Elevated AhR expression in lung adenocarcinoma cells could increase intracellular oxidative stress and promote cell growth, implying that disrupting AhR expression might prevent the early development of lung adenocarcinomas.

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“…mRNA levels of CYP1A1, CYP1B1, AhR, ARNT and ß-actin were evaluated by real-time PCR system 7500 (Applied Biosystems, Foster City, CA) using High Capacity cDNA Reverse Transcription Kit (Applied Biosystems) and FastStart Universal SYBR Green Master (ROX) (Roche, Basel, Switzerland). The primer sequences were described previously (21). Quantitative values were obtained from the threshold cycle (C t ) number.…”

Section: Methodsmentioning

confidence: 99%

CYP1B1, but not CYP1A1, is downregulated by promoter methylation in colorectal cancers

Habano¹

2009

Int J Oncol

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Abstract. Cytochrome P450 (CYP) 1A1 (CYP1A1) and CYP1B1, dioxin-inducible CYP1s, are associated with carcinogenesis in extrahepatic tissues. CYP1B1 is featured in carcinogenesis of hormone-responsive tissues, where the CYP1B1 level is considerably high. Although aberrant expression of these enzymes is also observed in cancers that are not related to hormone response, their roles in carcinogenesis are not yet fully understood. We examined DNA methylation status of the CpG islands within the 5'-flanking region of the CYP1B1 and CYP1A1 genes in 7 colorectal cancer cell lines and 40 primary colorectal cancers. By bisulfite-modified direct sequencing, CYP1B1 gene methylation was detected in 2 cell lines (SW48 and Caco-2) and 2 (5%) cancers, but not in corresponding normal tissues. Treatment of the cells with 5-aza-2'-deoxycytidine revealed a clear increase in the CYP1B1 mRNA levels in SW48 and Caco-2 cells, while the amount of methylated alleles decreased. Only HT29 cells showed a clear increase in CYP1A1 mRNA, although there were no apparent differences in methylation status among these cell lines. None of these cell lines showed significant change in mRNA levels of aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT), which are known to directly activate CYP1 transcription. This observation suggested that expression of CYP1B1, but not CYP1A1, was downregulated by promoter methylation rather than decreased expression of AhR/ARNT. In conclusion, CpG methylation of the CYP1B1 promoter region epigenetically regulates CYP1B1 expression during development of some colorectal cancers. Moreover, cancers with aberrant CYP1B1 expression might show altered response to procarcinogen metabolism and chemotherapy.

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Preferential Induction of CYP1A1 and CYP1B1 in CCSP-Positive Cells

Cited by 33 publications

References 49 publications

Arylhydrocarbon Receptor Activation in NCI-H441 Cells and C57BL/6 Mice

Arylhydrocarbon Receptor Activation in NCI-H441 Cells and C57BL/6 Mice

Requirement of Aryl Hydrocarbon Receptor Overexpression for CYP1B1 Up-Regulation and Cell Growth in Human Lung Adenocarcinomas

CYP1B1, but not CYP1A1, is downregulated by promoter methylation in colorectal cancers

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