Peroxiredoxins, a novel protein family in lung cancer

Peroxiredoxins, a novel protein family in lung cancer
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DOI:
10.1002/ijc.20294
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发表时间:
2004-09-10
影响因子:
6.4
通讯作者:
Kinnula, VL
Kinnula, VL
中科院分区:
医学1区
文献类型:
--
作者:
Lehtonen, ST;Svensk, AM;Kinnula, VL

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吸烟是肺癌的主要危险因素,它会导致活性氧的积累。这些对细胞防御、细胞增殖和细胞死亡具有多重影响。因此,可以假设参与氧化还原平衡调节剂的化合物在癌发生和肿瘤进展中起重要作用。在这里,我们已经评估了所有6个过氧化物酶(Prxs I-VI)在肺癌中的表达。Prxs代表具有分解过氧化氢能力的蛋白质家族;因此,它们可以参与细胞抗氧化防御,调节细胞增殖并增加培养细胞的耐药性。应用免疫组化方法对92例乳腺癌进行了研究,其中腺癌32例,鳞癌45例,小细胞癌9例,其它6例。此外,11例腺癌或鳞癌进行了Western分析和/或RT-PCR研究。通过免疫组化和/或RT-PCR评估,Prxs I、II、IV和VI在肺癌中特别升高。Western分析显示,与非恶性组织相比,Prxs I和IV在肿瘤中显著升高(分别为p = 0.04和0.002)。Prx在不同肿瘤亚型中的表达存在显著差异,最显著的是Prx IV表达,其主要与腺癌相关。Prx VI表达升高与高级别鳞状细胞癌相关(p = 0.03),Prx II表达升高与晚期肿瘤相关(p = 0.01)。我们的结果表明Prxs可能对肺癌的进展有影响。(C)2004 Wiley-Liss,Inc.
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. (C) 2004 Wiley-Liss, Inc.