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Journal of Neuro-Oncology

, Volume 137, Issue 2, pp 241–248 | Cite as

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

  • Noble Kumar Talari
  • Manas K. Panigrahi
  • Sailaja Madigubba
  • Prakash Babu PhanithiEmail author
Laboratory Investigation

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.

Keywords

Human meningioma Aryl hydrocarbon receptor (AHR) Kynurenine (KYN) Indoleamine 2, 3 dioxygenases (IDO) 

Notes

Acknowledgements

This work was supported by Grants from Department of Biotechnology [BT/PR18168/MED/29/1064/2016, BT/PR13111/MED/29/149/2009], Department of Science and Technology [SR/CSRI/196/2016, SB/EMEQ-257/2013], Universities with potential for excellence Phase II [UH/UPE-2/28/2015] New Delhi, Government of India. The authors wish to acknowledge help of Dr. Janaki, Kurnool Medical College, Andhra Pradesh-INDIA, for providing autopsy meninges for our study.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

Supplementary material

11060_2017_2730_MOESM1_ESM.tif (1.1 mb)
Supplementary material 1 (TIF 1078 KB) Fig. S1 AHR (~ 100 kD) protein expression in human meningioma (a) AHR and GAPDH immuno-blots. b Densitometry analysis of AHR immunoblot. The expression levels of GAPDH (~ 38 kD) was used as loading controls. Data are represented as mean ± SE n = 6 for CM (Control meninges); n = 10 for GI (Grade I meningioma); n = 8 for GII (Grade II meningioma) and n = 6 for GIII (Grade III meningioma). pa ≤ 0.05; pb 0.05, pc ≤ 0.05 (where a, b, and c refers to comparison with CM, GI, GII respectively.

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Authors and Affiliations

  1. 1.Department of Biotechnology & Bioinformatics, School of Life SciencesUniversity of HyderabadHyderabadIndia
  2. 2.Department of NeurosurgeryKIMSSecunderabadIndia
  3. 3.Laboratory of Neurochemistry, Department of Biotechnology & Bioinformatics, School of Life sciencesUniversity of HyderabadHyderabadIndia

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