Peroxiredoxins, a novel protein family in lung cancer

Abstract

Cigarette smoke, the major risk factor for lung cancer, induces an accumulation of reactive oxygen species. These have multiple effects on cell defense, cell proliferation and cell death. Thus, compounds involved in the regulators of redox balance can be hypothesized to play a fundamental role in both carcinogenesis and tumor progression. Here, we have evaluated the expressions of all 6 peroxiredoxins (Prxs I-VI) in lung carcinomas. Prxs represent a protein family with the capability of breaking down hydrogen peroxide; thus, they can participate in cellular antioxidant defense, regulate cell proliferation and increase drug resistance of cultured cells. Altogether 92 cases were investigated by immunohistochemistry, including 32 adenocarcinomas, 45 squamous cell, 9 small cell and 6 other carcinomas. Additionally, 11 cases with adenocarcinoma or squamous cell carcinoma were studied by Western analysis and/or by RT-PCR. Prxs I, II, IV and VI were particularly elevated in lung carcinomas as assessed by immunohistochemistry and/or RT-PCR. Western analysis revealed that Prxs I and IV were significantly elevated in tumors compared to nonmalignant tissue (p ‫؍‬ 0.04 and 0.002, respectively). There were remarkable variations in Prx expression in various tumor subtypes, the most striking being Prx IV expression, which was mainly associated with adenocarcinoma. Elevated Prx VI expression was associated with high-grade squamous cell carcinoma (p ‫؍‬ 0.03) and Prx II expression, with advanced tumor stage (p ‫؍‬ 0.01). Our results suggest that Prxs may have effects on the progression of lung cancer.

Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma

“…In primary bladder cancer, the PRDX1 and 6 expression levels were significantly elevated in non-progressed cases compared to the progressed cases (34). The overexpression of PRDX was also reported in human breast and lung cancer (16,35). In OSCC, Yanagawa et al studied PRDX1 expression for the first time and found low PRDX1expression levels to be associated with larger tumor masses, lymph node metastases and poorly-differentiated tumors (36).…”

Peroxiredoxin 6 Is a Potent Cytoprotective Enzyme in the Epidermis

“…20 In addition, strong expression of Prdx6 was observed in affected tissues of patients suffering from various diseases, including psoriasis, 19 sporadic JakobCreutzfeld disease, 45 Parkinson's disease, 46 Pick disease, 47 and cancer. 48 All these conditions are associated with enhanced levels of ROS. 49,50 Thus, the strong expression of Prdx6 in these diseases may be a mechanism to limit the severity of the condition.…”

Phospholipase A2 Activity of Peroxiredoxin 6 Promotes Invasion and Metastasis of Lung Cancer Cells

“…Importantly, analyses of patient samples have revealed a significant association between PRDX6 expression in breast cancer cells and lymph node metastasis (26). It was similarly reported that PRDX6 expression in lung cancer cells was significantly associated with high-grade dysplasia and tumor progression (23,29). Although these observations suggest that PRDX6 has the ability to support invasiveness and metastasis of the cancer cells analyzed, it is currently unclear whether such functions of PRDX6 depend on its enzymatic activities, although such information is essential for a better understanding of the mechanism of PRDX6 action in cancer cells.…”

“…Firstly, PRDX6 is often upregulated in malignant tissues of various human organs, including lung (23,24) and breast (25,26). Moreover, functional studies using analyses of RNA interference and overexpression suggest that PRDX6 does not simply act as a cytoprotective antioxidant enzyme but also supports the growth, invasiveness, and metastasis of breast cancer cells (27).…”