Droździk Agnieszka, Kowalczyk Robert, Jaworowska Ewa, Urasińska Elżbieta, Kurzawski Mateusz
Department of General Dentistry, Pomeranian Medical University, Szczecin, Poland.
Department of Maxillofacial Surgery, Pomeranian Medical University, Szczecin, Poland.
Med Sci Monit. 2015 Apr 30;21:1243-8. doi: 10.12659/MSM.892674.
Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, providing antioxidant responses.
The study was carried out in pleomorphic adenoma and control parotid gland tissues, investigating gene expression of NFE2L2, as well as KEAP1 (Kelch-like ECH-associated protein 1) and NQO1 (quinone oxidoreductase), at mRNA and protein (immunohistochemistry) levels. Functional evaluation of Nrf2 system in the parotid gland was evaluated in HSY cells (human parotid gland adenocarcinoma cells).
Pleomorphic adenoma specimens showed cytoplasmic and nuclear Nfr2 expression in epithelial cells, as well as more variable lower Nrf2 level in mesenchymal cells. In the parotid gland, Nrf2 was expressed in cytoplasm of serous, mucous, and duct cells. Nuclear Nrf2 expression was predominantly seen in serous cells, whereas mucous and duct cells were mostly negative. Comparable mRNA levels of NFE2L2 and NQO1 genes and significantly higher expression of KEAP1 in pleomorphic adenoma were seen. HSY cell incubation with oltipraz demonstrated significant elevation of NFE2L2 after 24 and 48 hours of stimulation, whereas NQO1 was elevated, but significantly only after 24 hours, and KEAP1 expression remained unchanged.
Summarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.
多形性腺瘤（良性混合瘤）是最常见的涎腺肿瘤之一。然而，其致癌过程尚未明确。本研究旨在明确核因子E2相关因子2（Nfr2）在多形性腺瘤病理中的作用。Nrf2调控的基因系统是最关键的细胞保护机制之一，可提供抗氧化反应。
本研究在多形性腺瘤和对照腮腺组织中进行，在mRNA和蛋白质（免疫组织化学）水平上研究NFE2L2以及KEAP1（ Kelch样ECH相关蛋白1）和NQO1（醌氧化还原酶）的基因表达。在HSY细胞（人腮腺腺癌细胞）中评估腮腺中Nrf2系统的功能。
多形性腺瘤标本显示上皮细胞中存在细胞质和细胞核Nfr2表达，间充质细胞中Nrf2水平较低且变化更大。在腮腺中，Nrf2在浆液性、黏液性和导管细胞的细胞质中表达。细胞核Nrf2表达主要见于浆液性细胞，而黏液性和导管细胞大多为阴性。多形性腺瘤中NFE2L2和NQO1基因的mRNA水平相当，KEAP1表达显著更高。用奥替普拉孵育HSY细胞后，刺激24小时和48小时后NFE2L2显著升高，而NQO1升高，但仅在24小时后显著，KEAP1表达保持不变。
综合体外和体内观察结果，可以说Nrf2可能在多形性腺瘤的病理过程中起作用。
