Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types.
Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types.
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DOI：
10.1371/journal.pone.0030132
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Casiano CA
中科院分区：
文献类型：
--
作者：
Basu A;Rojas H;Banerjee H;Cabrera IB;Perez KY;De León M;Casiano CA
氧化应激调节的信号通路与癌变和治疗抵抗有关。晶状体上皮源性生长因子p75 （LEDGF/p75）是一种转录共激活因子，可促进对应激诱导的细胞死亡的抵抗。这种蛋白与炎症和自身免疫性疾病、hiv -艾滋病和癌症有关。尽管LEDGF/p75作为一种应激生存癌蛋白正在出现，但关于其在人类肿瘤中的表达的信息却很少。目前的研究是为了评估其在人类癌症综合小组中的表达。在Oncomine癌症基因微阵列数据库和TissueScan癌症调查小组定量聚合酶链反应（Q-PCR）阵列中检测转录物表达。采用免疫组化（IHC）技术对1220例（985例肿瘤组织和235例正常组织）中含有1735个组织的肿瘤组织微阵列（tma）中的蛋白表达进行了评估。共分析了21种主要癌症类型。对Oncomine数据集中LEDGF/p75转录物表达的分析显示，17种肿瘤类型中有15种显著上调（肿瘤与正常相比）。tisescan Cancer Q-PCR阵列显示，LEDGF/p75转录物在前列腺癌、结肠癌、甲状腺癌和乳腺癌中的表达显著升高。免疫组化分析显示，相对于相应的正常组织，前列腺、结肠、甲状腺、肝脏和子宫肿瘤中LEDGF/p75蛋白水平显著升高。LEDGF/p75转录物或蛋白表达在多种肿瘤类型中均有升高。这些结果进一步确定了LEDGF/p75是一种癌症相关蛋白，并为正在进行的旨在了解其在特定人类癌症中表达的临床意义的研究提供了依据。
Oxidative stress-modulated signaling pathways have been implicated in carcinogenesis and therapy resistance. The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell death. This protein has been implicated in inflammatory and autoimmune conditions, HIV-AIDS, and cancer. Although LEDGF/p75 is emerging as a stress survival oncoprotein, there is scarce information on its expression in human tumors. The present study was performed to evaluate its expression in a comprehensive panel of human cancers. Transcript expression was examined in the Oncomine cancer gene microarray database and in a TissueScan Cancer Survey Panel quantitative polymerase chain reaction (Q-PCR) array. Protein expression was assessed by immunohistochemistry (IHC) in cancer tissue microarrays (TMAs) containing 1735 tissues representing single or replicate cores from 1220 individual cases (985 tumor and 235 normal tissues). A total of 21 major cancer types were analyzed. Analysis of LEDGF/p75 transcript expression in Oncomine datasets revealed significant upregulation (tumor vs. normal) in 15 out of 17 tumor types. The TissueScan Cancer Q-PCR array revealed significantly elevated LEDGF/p75 transcript expression in prostate, colon, thyroid, and breast cancers. IHC analysis of TMAs revealed significant increased levels of LEDGF/p75 protein in prostate, colon, thyroid, liver and uterine tumors, relative to corresponding normal tissues. Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types. These results further establish LEDGF/p75 as a cancer-related protein, and provide a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers.
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