title: The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.
abstract: OBJECTIVE
  Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors.
  
  
  METHODS
  The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer.
  
  
  RESULTS
  Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD.
  
  
  CONCLUSIONS
  Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma.
authors.affiliation: Department of General Dentistry, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland. Electronic address: agdro@pum.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Drozdzik
authors.affiliation: Department of Maxillofacial Surgery, Pomeranian Medical University, Powstancow Wlk 72, 70-111 Szczecin, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Kowalczyk
authors.affiliation: Department of Preclinical Conservative and Endodontic Dentistry, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Lipski
authors.affiliation: Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Łapczuk
authors.affiliation: Department of Pathomorphology, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Urasinska
authors.affiliation: Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurzawski
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D008949:Adenoma, Pleomorphic / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C497396:ARNT protein, human; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: AhR; Pleomorphic adenoma; Salivary gland tumor