Cancer Letters

Cancer Letters

Volume 145, Issues 1–2, 18 October 1999, Pages 127-132
Cancer Letters

Peroxiredoxin I expression in human thyroid tumors

https://doi.org/10.1016/S0304-3835(99)00243-8Get rights and content

Abstract

Peroxiredoxin I (Prx I) is newly discovered oxidative stress inducible protein, having a thioredoxin peroxidase activity. The Prx I expression level in 107 samples out of 60 thyroid lesions, including normal thyroid, tumors and thyroiditis including Graves’ disease were examined using immunoblotting. Prx I expression levels in follicular neoplasm (P=0.00005) and thyroiditis group (P=0.0037) were significantly higher than that of the control group, while papillary carcinoma group did not show statistical significance. Immunohistochemistry indicated that Prx I was in epithelial cells of thyroid follicles. These results suggest that Prx I is expected to be a candidate for novel tumor markers to discriminate tissue types of tumors.

Introduction

The peroxiredoxins (Prx) are a family of novel antioxidant proteins found in a wide variety of species, that act as functional members in various biological processes [1], [2], [3], [4], [5], [6], [7]. Some of these proteins are also called thioredoxin peroxidases (TPx) and have been demonstrated to have a hydrogen peroxidase function and to act by dimerization as a thio-specific antioxidants [1], [8]. This Prx group is divided into 3 subsets: Prx I, Prx II, and Prx III [9]. The product of the proliferating associated gene (Pag) which belongs to Prx I was isolated from a ras-transformed human mammary epithelial cell line [5]. It was reported as a physiological inhibitor of c-Abl tyrosine kinase activity [10]. Although it is associated with cell proliferation and oncogenes, no reports that investigated its expression in clinical samples of tumors or diseased tissue.

Natural killer enhancing factor (NKEF) and MSP23 also belong to Prx I. NKEF was identified as a soluble factor from RBC cytosol that mediates an enhancement of natural killer activity [6]. MSP23 is an oxidative stress protein discovered previously and cloned from murine peritoneal macrophages. Its transcription level rises in response to oxidative stress [4].

Oxidative stress and damage by free radicals have been implicated in several pathologic states including cancer [11]. Reactive oxygen species (ROS) have been conventionally considered to have carcinogenic potential [12] and to promote invasiveness [13]. In addition, mitogenic signaling is mediated by oxidants [14], and the TPx family participates in the signaling cascades initiated by growth factors and tumor necrosis factor-alpha (TNF-α) by regulating the intracellular concentration of H2O2 [15]. Therefore, we are interested in examining the relationship between oxidative stress and cancers, and in the role played by Prx. The reports cited above suggest that the Prx I group may be closely associated with many diseases including tumors and inflammatory conditions. However, Prx I has not been investigated in human clinical samples as a potential marker. In this study, we focused on clinically obtainted thyroid samples, and designed experiments to compare Prx I expression levels in tissues representing a number of thyroid diseases. Thyroid diseses have suggestive factors that are associated with Prx I expression. The oxidative stress is common in the thyroid tissue by utilization of H2O2 for thyroxine synthesis, the inflammation produces ROS, and the tumor has active proliferation. Here we present the first report that shows a relationship between the expression levels of Prx I and thyroid tumors and thyroiditis.

Section snippets

Patients and samples

This study was conducted from March (((( to January 1998 of Tsukuba University Hospital. One-hundred-and-seven surgical samples from 60 patients with thyroid lesions were selected. Ten of the patients were male, 50 were female, and the ages ranged from 21–89 years with a mean of 46.2 years. Whenever possible, a part of the normal contralateral lobe was also obtained as a control. The samples consisted of 50 from normal thyroid, 24 from papillary carcinomas, 17 from follicular neoplasm and 16

Immunoblotting and statistical analysis

A representative sample of our immunoblotting results is shown in Fig. 1. In every case a positive immunoreactive band was observed at or around 23 kDa. As controls, samples form the normal contralateral lobe of the thyroid were electrophoresed alongside the samples from diseased thyroid. In papillary carcinoma (lane 1), Prx I expression was lower than that of its control (lane 2), while the levels in follicular adenoma (lane 3) and follicular adenocarcinoma (lane 5) were higher than in their

Discussion

In this study, in the follicular neoplasm and focal thyroiditis groups, the expression of Prx I increased significantly, while the expression in papillary carcinoma was not significantly different from that of normal tissue. We tried to correlate the Prx I expression level with pathological change and clinical features, but no tendency was observed in this experiment.

One possible explanation for this result could be cellular response against oxidative stress. It follows from the fact that Prx I

Acknowledgements

Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture in Japan. The authors thank Drs. Tatsuro Shimokama, Yuji Aiyoshi, Ei Ueno, Tohru Yashiro and Masanao Miwa for valuable advice.

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