Differential expression of arrestins is a predictor of breast cancer progression and survival
Differential expression of arrestins is a predictor of breast cancer progression and survival
复制标题
DOI：
10.1007/s10549-011-1374-9
复制
发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Benovic, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Michal, Allison M.;Peck, Amy R.;Benovic, Jeffrey L.
新出现的证据表明，G蛋白偶联受体（例如CXCR 4和PAR2）与乳腺癌的进展和转移性乳腺癌的发展有关。然而，调节这些受体功能的蛋白质（如arrestins）在乳腺癌中的作用尚未确定。在各种乳腺癌细胞系中对两种非视觉抑制蛋白（抑制蛋白2和3）的表达进行检查，发现抑制蛋白3在基底细胞系和管腔细胞系中的表达相当，而抑制蛋白2在管腔细胞系中的表达远高于更具侵袭性的基底细胞系。正常人乳腺组织的分析显示，arrestin2和3在乳腺上皮的管腔和肌上皮细胞中表达，arrestin2在肌上皮细胞中最高，arrestin3在两种细胞类型中相当。免疫荧光定量检测发现，arrestin 2的表达随着乳腺癌从导管原位癌到浸润癌再到淋巴结转移而显著降低（P < 0.001）。此外，arrestin2表达降低与生存率降低（P = 0.0007）以及淋巴结阳性状态和肿瘤大小和核分级增加相关。相反，arrestin3表达在乳腺癌进展过程中显著增加（P < 0.001），并且表达增加与生存率降低相关（P = 0.014）。Arrestin3也是乳腺癌的独立预后标志物，风险比为1.65。总体而言，这些研究表明，在乳腺癌进展过程中，arrestin2水平降低，而arrestin3水平升高，这些变化与不良临床结局相关。
Emerging evidence has implicated G protein-coupled receptors, such as CXCR4 and PAR2, in breast cancer progression and the development of metastatic breast cancer. However, the role of proteins that regulate the function of these receptors, such as arrestins, in breast cancer has yet to be determined. Examination of the expression of the two nonvisual arrestins, arrestin2 and 3, in various breast cancer cell lines revealed comparable expression of arrestin3 in basal and luminal lines while arrestin2 expression was much higher in the luminal lines compared to the more aggressive basal lines. Analysis of normal human breast tissue revealed that arrestin2 and 3 were expressed in both luminal and myoepithelial cells of mammary epithelia with arrestin2 highest in myoepithelial cells and arrestin3 comparable in both cell types. Quantitative immunofluorescence-based examination of primary breast tumors revealed that arrestin2 expression significantly decreased with cancer progression from ductal carcinoma in situ to invasive carcinoma and further to lymph node metastasis (P < 0.001). Moreover, decreased arrestin2 expression was associated with decreased survival (P = 0.0007) as well as positive lymph node status and increased tumor size and nuclear grade. In contrast, arrestin3 expression significantly increased during breast cancer progression (P < 0.001) and increased expression was associated with decreased survival (P = 0.014). Arrestin3 was also an independent prognostic marker of breast cancer with a hazard ratio of 1.65. Overall, these studies demonstrate that arrestin2 levels decrease while arrestin3 levels increase during breast cancer progression and these changes correlate with a poor clinical outcome.