前列腺癌中的抗核自身抗体：对LEDGF/p75的免疫反应，LEDGF/p75是一种在前列腺肿瘤中高度表达且在细胞凋亡过程中被切割的存活蛋白。

Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis.

作者信息

Daniels Tracy, Zhang Jianying, Gutierrez Israel, Elliot Max L, Yamada Brian, Heeb Mary Jo, Sheets Shaun M, Wu Xiwei, Casiano Carlos A

机构信息

Loma Linda University School of Medicine, Department of Biochemistry and Microbiology and Center for Molecular Biology and Gene Therapy, 11085 Campus Street, Loma Linda, CA 92350, USA.

出版信息

Prostate. 2005 Jan 1;62(1):14-26. doi: 10.1002/pros.20112.

DOI:10.1002/pros.20112

PMID:15389814

Abstract

BACKGROUND

Cancer patients produce autoantibodies to self-proteins called tumor-associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa).

METHODS

Serum autoantibodies to the survival protein lens epithelium-derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting.

RESULTS

Anti-LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P < 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells.

CONCLUSIONS

The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients.

摘要

背景

癌症患者会产生针对称为肿瘤相关抗原（TAA）的自身蛋白的自身抗体。这些自身抗体是识别新型生物标志物和治疗靶点的潜在有价值工具。本研究旨在鉴定前列腺癌（PCa）中的TAA。

方法

通过免疫荧光显微镜、酶联免疫吸附测定（ELISA）和免疫印迹法检测针对存活蛋白晶状体上皮衍生生长因子p75（LEDGF/p75）的血清自身抗体。通过免疫印迹或免疫组织化学评估LEDGF/p75在前列腺细胞和肿瘤中的表达。通过免疫印迹法检测LEDGF/p75的凋亡切割。

结果

ELISA检测发现，18.4%的PCa患者和5.5%的匹配对照中存在抗LEDGF/p75自身抗体（P<0.001），而良性前列腺增生（BPH）患者中未检测到。93%的前列腺肿瘤中检测到LEDGF/p75表达，而正常前列腺中未检测到。61%的前列腺肿瘤中观察到该蛋白的强表达。BPH组织中也检测到中度至高表达。在凋亡的前列腺细胞中检测到LEDGF/p75的切割。