Clinic of Obstetrics and Gynecology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, D-45147 Essen, Germany.
Anticancer Res. 2011 Jun;31(6):2197-201.
Recent data suggest a role of the ubiquitin-proteasome system in various malignancies. In patients with neoplasms, increased extracellular concentrations of circulating 20S proteasome (c-proteasome) have been detected in blood plasma. We tested the hypothesis that the plasma c-proteasome concentration is a biomarker associated with tumor stage and nodal status in patients with the primary diagnosis of non-metastatic breast cancer.
Venous plasma concentration of 20S proteasome was measured by ELISA technique in 224 non-metastatic breast cancer patients and in 50 healthy volunteers. To assess the relation of proteasome expression to c-proteasome concentration, tumor specimens from 32 patients were immunohistochemically stained for 20S proteasome using an antibody directed against the core subunits of the catalytic domain of the 20S proteasome.
The median c-proteasome concentration was higher (p<0.0001) in breast cancer patients (397.5 ng/ml, range: 200-50,000 ng/ml) than in healthy controls (305 ng/ml, range: 140-425 ng/ml). There was no significant correlation between c-proteasome concentration and strength of proteasomal staining in tumor specimens. Neither tumor size, nor nodal status, nor any other prognostically important clinical parameter, including the presence of disseminated tumor cells in the bone marrow, correlated with high c-proteasome concentrations.
Circulating proteasome concentrations appear to be higher in patients presenting with primary breast cancer than in healthy controls. Thus, the ubiquitin-proteasome system might represent a potential target in breast cancer treatment.
最近的数据表明泛素-蛋白酶体系统在各种恶性肿瘤中起作用。在肿瘤患者中，血浆中循环 20S 蛋白酶体（c-proteasome）的细胞外浓度增加。我们检验了这样一个假设，即在原发性非转移性乳腺癌患者中，血浆 c-proteasome 浓度与肿瘤分期和淋巴结状态有关。
通过 ELISA 技术测量了 224 例非转移性乳腺癌患者和 50 例健康志愿者的静脉血浆 20S 蛋白酶体浓度。为了评估蛋白酶体表达与 c-proteasome 浓度的关系，使用针对 20S 蛋白酶体催化结构域核心亚基的抗体对 32 例患者的肿瘤标本进行了免疫组织化学染色。
c-proteasome 浓度中位数在乳腺癌患者中较高（p<0.0001）（397.5ng/ml，范围：200-50000ng/ml），明显高于健康对照组（305ng/ml，范围：140-425ng/ml）。肿瘤标本中 c-proteasome 浓度与蛋白酶体染色强度之间无显著相关性。肿瘤大小、淋巴结状态或任何其他预后重要的临床参数（包括骨髓中播散性肿瘤细胞的存在）均与高 c-proteasome 浓度无关。
与健康对照组相比，原发性乳腺癌患者的循环蛋白酶体浓度似乎更高。因此，泛素-蛋白酶体系统可能是乳腺癌治疗的潜在靶点。
