Abstract
The enzyme paraoxonase-2 (PON2) is ubiquitously expressed and exerts its antiapoptotic and antioxidative functions in several intracellular compartments.The aim of this study is to investigate the role of PON2 in bladder cancer (BC). The expression levels of PON2 in paired tumor and normal bladder tissue samples and in urinary exfoliated cells from patients affected with BC and healthy donors were evaluated. Moreover, the effect of PON2 overexpression on tumor cell proliferation and susceptibility to oxidative stress was investigated in human bladder cancer cell line T24.Our results showed that PON2 expression levels were significantly higher in BC compared with non-tumor tissue. In urinary exfoliated cells from BC patients, PON2 mRNA levels showed an inverse correlation with tumor stage (pT). Moreover, PON2 overexpression in T24 cells led to a significant increase in tumor cell proliferation and resistance to oxidative stress.The results obtained showed that PON2 could represent a molecular biomarker for bladder cancer and suggest a potential role of the enzyme as a prognostic factor for this neoplasm.
Highlights
Paraoxonase-2 (PON2), a member of the multigene family of paraoxonases (PONs), is expressed in various tissues and cells
Results obtained from Real-Time PCR analyses performed on tissue samples showed that PON2 expression levels were significantly (p
In patients affected with BC, urinary PON2 expression levels did not correlate with gender (p=0.783), age (p=0.644) and histological grading (p=0.488) (Table 1)
Summary
Paraoxonase-2 (PON2), a member of the multigene family of paraoxonases (PONs), is expressed in various tissues and cells. PON2 exerts its functions in intracellular environment [1,2,3]. PON2 is localized in mitochondria, in endoplasmatic reticulum (ER) and in nuclear lamina. Till upregulated levels of PON2 have been detected in different types of cancer cells, such as hepatocellular carcinoma, prostate cancer and pediatric acute lymphoblastic leukemia, and it has been suggested a possible involvement of PON2 in apoptotic escape of tumor cells [6, 13,14,15]. PON2 knockdown in the tumor cell lines K562 (leukemia) and A549 (lung cancer) initiated apoptosis [6], suggesting that PON2 may act as a target for cancer therapy in certain malignancies and fulfill an outstanding function for tumor cell survival
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