Suzuki Takashi, Urano Tomohiro, Miki Yasuhiro, Moriya Takuya, Akahira Jun-ichi, Ishida Takanori, Horie Kuniko, Inoue Satoshi, Sasano Hironobu
Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, 980-8575, Japan.
Cancer Sci. 2007 May;98(5):644-51. doi: 10.1111/j.1349-7006.2007.00444.x. Epub 2007 Mar 14.
Cyclin B1 is translocated to the nucleus from the cytoplasm, and plays an essential role in cell proliferation through promotion of mitosis. Although overexpression of cyclin B1 was previously reported in breast carcinomas, the biological significance of the intracellular localization of cyclin B1 remains unclear. Therefore, in this study, we examined cyclin B1 immunoreactivity in 109 breast carcinomas, according to the intracellular localization, that is, nucleus, cytoplasm or total (nucleus or cytoplasm). Total cyclin B1 was detected in carcinoma cells in 42% of breast carcinomas examined, whereas nuclear and cytoplasmic cyclin B1 were positive in 17 and 35% of the cases, respectively. Total or cytoplasmic cyclin B1 were positively associated with histological grade, mitosis, Ki-67, p53, c-myc or 14-3-3sigma, and inversely correlated with estrogen or progesterone receptor. Nuclear cyclin B1 was significantly associated with tumor size, lymph node metastasis, histological grade, mitosis, Ki-67 or polo-like kinase 1. Only nuclear cyclin B1 was significantly associated with adverse clinical outcome of the patients, and multivariate analyses of disease-free and overall survival demonstrated nuclear cyclin B1 as the independent marker. A similar tendency was detected in the patients receiving adjuvant therapy after surgery. These results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo-like kinase 1 and 14-3-3sigma. Nuclear cyclin B1-positive breast carcinoma is resistant to adjuvant therapy, and nuclear cyclin B1 immunoreactivity is a potent prognostic factor in breast carcinoma patients.
细胞周期蛋白B1（Cyclin B1）从细胞质转运至细胞核，并通过促进有丝分裂在细胞增殖中发挥重要作用。尽管先前报道过细胞周期蛋白B1在乳腺癌中过表达，但其细胞内定位的生物学意义仍不清楚。因此，在本研究中，我们根据细胞内定位，即细胞核、细胞质或总定位（细胞核或细胞质），检测了109例乳腺癌中的细胞周期蛋白B1免疫反应性。在所检测的乳腺癌中，42%的癌细胞中检测到总细胞周期蛋白B1，而细胞核和细胞质中的细胞周期蛋白B1阳性率分别为17%和35%。总细胞周期蛋白B1或细胞质细胞周期蛋白B1与组织学分级、有丝分裂、Ki-67、p53、c-myc或14-3-3σ呈正相关，与雌激素或孕激素受体呈负相关。细胞核细胞周期蛋白B1与肿瘤大小、淋巴结转移、组织学分级、有丝分裂、Ki-67或polo样激酶1显著相关。只有细胞核细胞周期蛋白B1与患者的不良临床结局显著相关，无病生存期和总生存期的多因素分析表明细胞核细胞周期蛋白B1是独立标志物。在术后接受辅助治疗的患者中也检测到类似趋势。这些结果表明，过表达的细胞周期蛋白B1的致癌作用主要在乳腺癌细胞核中介导，且核转位受polo样激酶1和14-3-3σ调节。细胞核细胞周期蛋白B1阳性的乳腺癌对辅助治疗耐药，细胞核细胞周期蛋白B1免疫反应性是乳腺癌患者的有力预后因素。
