Increased PADI4 expression in blood and tissues of patients with malignant tumors.
Increased PADI4 expression in blood and tissues of patients with malignant tumors.
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DOI：
10.1186/1471-2407-9-40
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发表时间：
2009-01-30
期刊：
影响因子：
3.8
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Chang X;Han J;Pang L;Zhao Y;Yang Y;Shen Z
PAD4/PADI4翻译后将多肽精氨酸转化为瓜氨酸。最近的研究表明，PADI4通过组蛋白在基因启动子上的瓜氨酸化来抑制P53调控基因的表达。应用免疫组织化学、实时荧光定量聚合酶链式反应和免疫印迹技术检测PADI4在不同肿瘤和非肿瘤组织(n=1673)以及A549、SKOV3和U937肿瘤细胞系中的表达。用双抗体夹心ELISA法检测了1121例肿瘤患者血中PADI4和瓜氨酸抗凝血酶(CAT)水平。免疫组织化学检测到PADI4在乳腺癌、肺腺癌、肝细胞癌、食管鳞癌、结直肠癌、肾癌细胞、卵巢腺癌、子宫内膜癌、子宫腺癌、膀胱癌、软骨瘤以及其他转移性癌中均有显著表达。PADI4在良性胃肌瘤、子宫肌瘤、子宫内膜增生症、宫颈息肉、畸胎瘤、葡萄胎、滋养细胞增生症、舌样腺瘤、血管瘤、淋巴组织增生症、神经鞘瘤、神经纤维瘤、脂肪瘤和肝海绵状血管瘤中均未见表达。此外，PADI4在胆囊炎、宫颈炎症、骨性关节炎滑膜炎等非肿瘤组织中未见表达，在胃炎、阑尾炎等急性炎症组织中未检测到PADI4的表达。定量聚合酶链式反应和免疫印迹分析显示PADI4在胃腺癌、肺腺癌、肝细胞癌、食管鳞癌和乳腺癌(每种疾病各5例)中的表达高于癌旁正常组织。此外，免疫印迹分析检测到PADI4在培养的肿瘤细胞系中的表达。ELISA法检测到各种恶性肿瘤患者的血液中PADI4和CAT水平均高于慢性炎症和良性肿瘤患者。这与免疫组织化学结果一致。此外，PADI4和CAT水平与较高的已知肿瘤标志物水平显著相关。我们的结果表明，PADI4在许多恶性肿瘤的血液和组织中的表达增加，这一发现有助于进一步了解肿瘤的发生。
Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients with chronic inflammation and benign tumors. This was consistent with immunohistochemical results. Additionally, PADI4 and cAT levels were significantly associated with higher levels of known tumor markers. Our results suggest that PADI4 expression is increased in the blood and tissues of many malignant tumors, a finding useful for further understanding of tumorigenesis.
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影响因子：
2.3
作者：
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期刊：
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影响因子：
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通讯作者：
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影响因子：
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