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Published in: Journal of Neuro-Oncology 2/2018

01-04-2018 | Laboratory Investigation

Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma

Authors: Noble Kumar Talari, Manas K. Panigrahi, Sailaja Madigubba, Prakash Babu Phanithi

Published in: Journal of Neuro-Oncology | Issue 2/2018

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Abstract

Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor and involved in tumorigenesis of many cancers. However there are no reports on AHR in human meningioma. Therefore we examined the status of the AHR and its signalling molecules in human meningioma by using tumor biopsy samples and autopsy control meninges. We report the up regulation of AHR pathway genes like aryl hydrocarbon receptor nuclear translocator (ARNT), aldehyde dehydrogenase1family memberA3 (ALDH1A3), cytochrome P450, family1, subfamily A polypeptide1 (CYP1A1) and TCCD induced poly ADP ribose polymerase (TIPARP) gene expression in human meningioma. Further, AHR protein expression was found to be up regulated in all grades of human meningioma. We found that AHR localized in the nucleus for high grade anaplastic meningioma through immunohistochemical analysis. Since AHR signalling pathway was known to involve in inhibition of apoptosis in cancer cells, we evaluated the cyclophilin D levels which maintains mitochondrial permeability transition pore a critical event during apoptosis. We report that cyclophilin D levels were upregulated in all grades of human meningioma compared to control meninges. Finally we also evaluated c-Fos protein levels as its levels were regulated by AHR. Here we report that c-Fos protein levels were down regulated in all grades of human meningioma compared to control meninges. To sum-up we found that AHR signalling pathway components were upregulated, as the grade of the meningioma progresses from low to high grade, suggesting an important role of AHR signalling pathway in human meningioma.
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Literature
3.
go back to reference Su JM, Lin P, Wang CK, Chang H (2009) Overexpression of cytochrome P450 1B1 in advanced non-small cell lung cancer: a potential therapeutic target. Anticancer Res 29:509–515PubMed Su JM, Lin P, Wang CK, Chang H (2009) Overexpression of cytochrome P450 1B1 in advanced non-small cell lung cancer: a potential therapeutic target. Anticancer Res 29:509–515PubMed
7.
go back to reference Peng TL, Chen J, Mao W, Liu X, Tao Y, Chen LZ, Chen MH (2009) Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer. World J Gastroenterol 15:1719–1729CrossRefPubMedPubMedCentral Peng TL, Chen J, Mao W, Liu X, Tao Y, Chen LZ, Chen MH (2009) Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer. World J Gastroenterol 15:1719–1729CrossRefPubMedPubMedCentral
8.
go back to reference Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehmann I, von Deimling A, Wick W, Platten M (2011) An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478:197–203. https://doi.org/10.1038/nature10491 CrossRefPubMed Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehmann I, von Deimling A, Wick W, Platten M (2011) An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478:197–203. https://​doi.​org/​10.​1038/​nature10491 CrossRefPubMed
11.
go back to reference Perdew GH, Bradfield CA (1996) Mapping the 90 kDa heat shock protein binding region of the Ah receptor. Biochem Mol Biol Int 39:589–593PubMed Perdew GH, Bradfield CA (1996) Mapping the 90 kDa heat shock protein binding region of the Ah receptor. Biochem Mol Biol Int 39:589–593PubMed
12.
go back to reference Kazlauskas A, Poellinger L, Pongratz I (1999) Evidence that the co-chaperone p23 regulates ligand responsiveness of the dioxin (Aryl hydrocarbon) receptor. J Biol Chem 274:13519–13524CrossRefPubMed Kazlauskas A, Poellinger L, Pongratz I (1999) Evidence that the co-chaperone p23 regulates ligand responsiveness of the dioxin (Aryl hydrocarbon) receptor. J Biol Chem 274:13519–13524CrossRefPubMed
13.
go back to reference Enan E, Matsumura F (1996) Identification of c-Src as the integral component of the cytosolic Ah receptor complex, transducing the signal of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the protein phosphorylation pathway. Biochem Pharmacol 52:1599–1612CrossRefPubMed Enan E, Matsumura F (1996) Identification of c-Src as the integral component of the cytosolic Ah receptor complex, transducing the signal of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the protein phosphorylation pathway. Biochem Pharmacol 52:1599–1612CrossRefPubMed
19.
go back to reference Zaher H, Fernandez-Salguero PM, Letterio J, Sheikh MS, Fornace AJ Jr, Roberts AB, Gonzalez FJ (1998) The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis. Mol Pharmacol 54:313–321CrossRefPubMed Zaher H, Fernandez-Salguero PM, Letterio J, Sheikh MS, Fornace AJ Jr, Roberts AB, Gonzalez FJ (1998) The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis. Mol Pharmacol 54:313–321CrossRefPubMed
20.
go back to reference Schubert A, Grimm S (2004) CyclophilinD, a component of the permeability transition-pore, is an apoptosis repressor. Cancer Res 64:85–93CrossRefPubMed Schubert A, Grimm S (2004) CyclophilinD, a component of the permeability transition-pore, is an apoptosis repressor. Cancer Res 64:85–93CrossRefPubMed
23.
go back to reference Bradford MM (1976) A rapid and sensitivemethod for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed Bradford MM (1976) A rapid and sensitivemethod for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed
28.
go back to reference Ishida M, Mikami S, Kikuchi E, Kosaka T, Miyajima A, Nakagawa K, Mukai M, Okada Y, Oya M (2010) Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer. Carcinogenesis 31:287 – 95. https://doi.org/10.1093/carcin/bgp222 CrossRefPubMed Ishida M, Mikami S, Kikuchi E, Kosaka T, Miyajima A, Nakagawa K, Mukai M, Okada Y, Oya M (2010) Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer. Carcinogenesis 31:287 – 95. https://​doi.​org/​10.​1093/​carcin/​bgp222 CrossRefPubMed
30.
go back to reference Lin P, Chang H, Tsai WT, Wu MH, Liao YS, Chen JT, Su JM (2003) Overexpression of aryl hydrocarbon receptor in humanlungcarcinomas. Toxicol Pathol 31:22–30CrossRefPubMed Lin P, Chang H, Tsai WT, Wu MH, Liao YS, Chen JT, Su JM (2003) Overexpression of aryl hydrocarbon receptor in humanlungcarcinomas. Toxicol Pathol 31:22–30CrossRefPubMed
32.
go back to reference Hayashibara T, Yamada Y, Mori N, Harasawa H, Sugahara K, Miyanishi T, Kamihira S, Tomonaga M (2003) Possible involvement of aryl hydrocarbon receptor (AhR) in adult T-cell leukemia (ATL) leukemogenesis: constitutive activation of AhR in ATL. Biochem Biophys Res Commun 300:128 – 34CrossRefPubMed Hayashibara T, Yamada Y, Mori N, Harasawa H, Sugahara K, Miyanishi T, Kamihira S, Tomonaga M (2003) Possible involvement of aryl hydrocarbon receptor (AhR) in adult T-cell leukemia (ATL) leukemogenesis: constitutive activation of AhR in ATL. Biochem Biophys Res Commun 300:128 – 34CrossRefPubMed
37.
go back to reference Kong B, Wu W, Cheng T, Schlitter AM, Qian C, Bruns P, Jian Z, Jäger C, Regel I, Raulefs S, Behler N, Irmler M, Beckers J, Friess H, Erkan M, Siveke JT, Tannapfel A, Hahn SA, Theis FJ, Esposito I, Kleeff J, Michalski CW (2016) A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling. Gut 65:647–657. https://doi.org/10.1136/gutjnl-2014-307616 CrossRefPubMed Kong B, Wu W, Cheng T, Schlitter AM, Qian C, Bruns P, Jian Z, Jäger C, Regel I, Raulefs S, Behler N, Irmler M, Beckers J, Friess H, Erkan M, Siveke JT, Tannapfel A, Hahn SA, Theis FJ, Esposito I, Kleeff J, Michalski CW (2016) A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling. Gut 65:647–657. https://​doi.​org/​10.​1136/​gutjnl-2014-307616 CrossRefPubMed
38.
go back to reference Jia J, Parikh H, Xiao W, Hoskins JW, Pflicke H, Liu X, Collins I, Zhou W, Wang Z, Powell J, Thorgeirsson SS, Rudloff U, Petersen GM, Amundadottir LT (2013) An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer. BMC Med Genom 6:33. https://doi.org/10.1186/1755-8794-6-33 CrossRef Jia J, Parikh H, Xiao W, Hoskins JW, Pflicke H, Liu X, Collins I, Zhou W, Wang Z, Powell J, Thorgeirsson SS, Rudloff U, Petersen GM, Amundadottir LT (2013) An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer. BMC Med Genom 6:33. https://​doi.​org/​10.​1186/​1755-8794-6-33 CrossRef
40.
go back to reference Marcato P, Dean CA, Pan D, Araslanova R, Gillis M, Joshi M, Helyer L, Pan L, Leidal A, Gujar S, Giacomantonio CA, Lee PW (2011) Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis. Stem Cells 29:32–45. https://doi.org/10.1002/stem.563 CrossRefPubMed Marcato P, Dean CA, Pan D, Araslanova R, Gillis M, Joshi M, Helyer L, Pan L, Leidal A, Gujar S, Giacomantonio CA, Lee PW (2011) Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis. Stem Cells 29:32–45. https://​doi.​org/​10.​1002/​stem.​563 CrossRefPubMed
Metadata
Title
Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma
Authors
Noble Kumar Talari
Manas K. Panigrahi
Sailaja Madigubba
Prakash Babu Phanithi
Publication date
01-04-2018
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2730-3

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