Cui Junwei, Li Peng, Liu Xiaoling, Hu Hui, Wei Wei
Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
Oncol Lett. 2015 Apr;9(4):1600-1606. doi: 10.3892/ol.2015.2942. Epub 2015 Feb 9.
Previous studies have reported that breast cancer stem cells may be closely associated with tumor metastasis, recurrence, and even the failure of chemotherapy and radiotherapy. The aim of the present study was to investigate whether important cell signaling pathways associated with drug resistance are activated in stem-like acetaldehyde dehydrogenase (ALDH) cluster of differentiation (CD)44 cells, and to analyze the association between ALDHCD44 cells and specific pathological features. ALDHCD44 cells and non-stem-like ALDHCD44 cells were separated from MDA-MB-231 cells by fluorescence-activated cell sorting, and the mRNA expression levels of Notch1 and β-catenin were estimated by performing quantitative polymerase chain reaction in the stem-like and non-stem-like cells. Line correlation analysis was used to evaluate the correlation between an immunohistochemical panel of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67, and ALDHCD44 cells from patients with invasive breast carcinoma. The mRNA levels of Notch1 and β-catenin were significantly higher in the ALDHCD44 cells compared with those in the ALDHCD44 cells (P<0.05); furthermore, the present study determined a high correlation (P<0.05) between the ALDHCD44 cells and Ki-67 expression (P=0.007), but no correlation (P≥0.05) with ER (P=0.065), PR (P=0.107) and HER2 (P=0.050). Overall, these data clearly indicate that ALDHCD44 cells may serve as novel diagnostic and prognostic factors in breast cancer.
以往研究报道,乳腺癌干细胞可能与肿瘤转移、复发,甚至放化疗失败密切相关。本研究旨在探讨与耐药相关的重要细胞信号通路在乙醛脱氢酶(ALDH)分化簇(CD)44干细胞样细胞中是否被激活,并分析ALDHCD44细胞与特定病理特征之间的关联。通过荧光激活细胞分选从MDA-MB-231细胞中分离出ALDHCD44细胞和非干细胞样ALDHCD44细胞,并通过定量聚合酶链反应检测干细胞样细胞和非干细胞样细胞中Notch1和β-连环蛋白的mRNA表达水平。采用线性相关分析评估雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)和Ki-67免疫组化指标与浸润性乳腺癌患者ALDHCD44细胞之间的相关性。与非ALDHCD44细胞相比,ALDHCD44细胞中Notch1和β-连环蛋白的mRNA水平显著更高(P<0.05);此外,本研究确定ALDHCD44细胞与Ki-67表达之间存在高度相关性(P<0.05)(P=0.007),但与ER(P=0.065)、PR(P=0.107)和HER2(P=0.050)无相关性(P≥0.05)。总体而言,这些数据清楚地表明,ALDHCD44细胞可能作为乳腺癌新的诊断和预后因素。