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侵蚀性类风湿性滑膜组织中p53肿瘤抑制基因的突变

Mutations of the p53 tumour suppressor gene in erosive rheumatoid synovial tissue.

作者信息

Rème T, Travaglio A, Gueydon E, Adla L, Jorgensen C, Sany J

机构信息

Unité INSERM U291, Hôpital Lapeyronie, Montpellier, France.

出版信息

Clin Exp Immunol. 1998 Feb;111(2):353-8. doi: 10.1046/j.1365-2249.1998.00508.x.

DOI:10.1046/j.1365-2249.1998.00508.x
PMID:9486403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1904928/
Abstract

Erosive rheumatoid arthritis (RA) is accompanied by synovial tissue hyperplasia associated with the proliferation of transformed-appearing synovial lining cells. In the present study we have analysed the expression of the p53 tumour suppressor gene in the synovial pannus tissue from patients at various stages of the disease. We used a combination of polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) on DNA and reverse transcription, PCR and sequencing on cDNAs from synovial tissues or purified synovial cell populations of 24 RA and three osteoarthritis (OA) patients. We also studied p53 expression by immunohistochemical analysis. Mutations suspected after SSCP were identified by systematic sequencing of the p53 exon 6, especially in the fibroblast-like, adherent synovial cell population, associated with an erosive disease. Some accumulation of the protein was detected in immunohistochemical analysis of the p53 tumour suppressor gene in the patients' synovial tissues. However, no sign of malignancy was seen in these patients after a 2-year survey. These results show some abnormalities in the p53 tumour suppressor gene in RA patients, but do not allow this to be related to characteristic proliferative features of the rheumatoid synovium.

摘要

侵蚀性类风湿关节炎(RA)伴有滑膜组织增生,这与形态改变的滑膜衬里细胞增殖有关。在本研究中,我们分析了处于疾病不同阶段的患者滑膜血管翳组织中p53肿瘤抑制基因的表达情况。我们对24例RA患者和3例骨关节炎(OA)患者的滑膜组织或纯化的滑膜细胞群体的DNA进行聚合酶链反应(PCR)和单链构象多态性(SSCP)分析,并对cDNA进行逆转录、PCR和测序。我们还通过免疫组织化学分析研究了p53的表达。通过对p53外显子6进行系统测序来鉴定SSCP后怀疑的突变,特别是在与侵蚀性疾病相关的成纤维细胞样贴壁滑膜细胞群体中。在患者滑膜组织中对p53肿瘤抑制基因进行免疫组织化学分析时检测到了一些蛋白质积累。然而,经过2年的调查,这些患者未出现恶性迹象。这些结果表明RA患者的p53肿瘤抑制基因存在一些异常,但这与类风湿滑膜的特征性增殖特征无关。

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