Drozdzik Agnieszka, Kowalczyk Robert, Lipski Mariusz, Łapczuk Joanna, Urasinska Elzbieta, Kurzawski Mateusz
Department of General Dentistry, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
Department of Maxillofacial Surgery, Pomeranian Medical University, Powstancow Wlk 72, 70-111 Szczecin, Poland.
Arch Oral Biol. 2016 Jan;61:53-9. doi: 10.1016/j.archoralbio.2015.10.016. Epub 2015 Oct 22.
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.
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.
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.
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.
多形性腺瘤（良性混合瘤）是最常见的唾液腺肿瘤之一。然而，其发生发展所涉及的分子机制尚未完全明确。因此，本研究旨在明确芳烃受体（AhR）在多形性腺瘤病理过程中的作用，因为有文献记载AhR调控的基因系统在多种人类肿瘤的发生中发挥作用。
本研究在多形性腺瘤组织和对照腮腺组织中进行，研究了AHR、AhR核转运蛋白（ARNT）、AhR阻遏蛋白（AHRR）以及AhR调控基因CYP1A1和CYP1B1在mRNA和蛋白质（免疫组织化学）水平的基因表达。以2,3,7,8-四氯二苯并对二恶英（TCDD）作为AhR特异性诱导剂，在HSY细胞（人腮腺腺癌细胞）中评估AhR系统的功能。
多形性腺瘤标本显示上皮细胞和间充质细胞的细胞质和细胞核中均有AhR表达。在腮腺中，AhR表达于导管细胞的细胞质中。与健康腮腺相比，多形性腺瘤组织中mRNA水平的定量表达显示AHR、ARNT和CYP1B1的表达显著更高，而CYP1A1水平相当。HSY细胞研究显示，与MCF-7细胞（用作对照的人乳腺腺癌细胞系）相比，HSY细胞中AHRR的表达水平显著更高。TCDD刺激后，观察到HSY细胞中AHRR水平下降，而MCF-7细胞中AHRR水平升高。TCDD对HSY和MCF-7细胞的增殖率（通过WST-1试验测定）没有影响。
综合体外和体内观察结果，可以认为AhR系统可能在多形性腺瘤的病理过程中发挥作用。
