The Role of Nrf2 in Pathology of Pleomorphic Adenoma in Parotid Gland

Background: 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.
Material and Methods: 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).
Results: 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.
Conclusions: Summarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.

Keywords: Adenoma, Pleomorphic - pathology, Epithelial Cells - pathology, Intracellular Signaling Peptides and Proteins - metabolism, NAD(P)H Dehydrogenase (Quinone) - genetics, NF-E2-Related Factor 2 - metabolism, Parotid Neoplasms - pathology, RNA, Messenger - metabolism, RNA, Neoplasm - metabolism, Tumor Cells, Cultured