Schindl Monika, Gnant Michael, Schoppmann Sebastian F, Horvat Reinhard, Birner Peter
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Anticancer Res. 2007 Mar-Apr;27(2):949-52.
Cul-4, a member of the Caenorhabditis elegans "cullin" ubiquitin-ligase gene family, plays a critical role in regulation of DNA-replication in this nematode. It has been suggested that cul-4 might have an important role in the development and progression of human cancer, but no data on this subject exist. The aim of this study was to investigate the expression and prognostic relevance of CUL-4 protein in lymph node-negative breast cancer, one of the most common malignancies worldwide.
CUL-4 protein expression was determined with immunohistochemistry in 167 specimens of human node-negative invasive breast cancer with long-term follow-up. Results were correlated with overall and disease-free survival of patients.
Strong expression of CUL-4 protein was observed in 32 cases (19.2%), moderate expression in 59 (35.3%), weak expression in 64 (38.3%), and in 12 tumors (7.2%) no expression of CUL4 was observed. Patients with strong expression of CUL4 had a significantly shorter overall and disease-free survival (p = 0.04 and p = 0.029, respectively; Cox regression) compared to all other cases.
Our data provide evidence for the first time that CUL-4 could play an important role in the development and progression of human cancer.
Cul-4是秀丽隐杆线虫“cullin”泛素连接酶基因家族的成员之一，在该线虫的DNA复制调控中起关键作用。有人提出cul-4可能在人类癌症的发生和发展中起重要作用，但目前尚无关于这一主题的数据。本研究的目的是调查CUL-4蛋白在淋巴结阴性乳腺癌（全球最常见的恶性肿瘤之一）中的表达及其与预后的相关性。
采用免疫组织化学方法检测167例长期随访的人淋巴结阴性浸润性乳腺癌标本中CUL-4蛋白的表达。结果与患者的总生存期和无病生存期相关。
在32例（19.2%）中观察到CUL-4蛋白强表达，59例（35.3%）中表达中等，64例（38.3%）中表达弱，12例肿瘤（7.2%）中未观察到CUL4表达。与所有其他病例相比，CUL4强表达的患者总生存期和无病生存期显著缩短（分别为p = 0.04和p = 0.029；Cox回归）。
我们的数据首次证明CUL-4可能在人类癌症的发生和发展中起重要作用。
