Department of Biomolecular Chemistry, Institute for Molecules and Materials and Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen - The Netherlands.
Int J Biol Markers. 2013 Dec 17;28(4):e365-70. doi: 10.5301/jbm.5000032.
αB-crystallin is regarded as a biomarker for triple-negative and/or basal-like breast cancer. In normal breast cells, overexpression of αB-crystallin leads to neoplastic-like changes, which likely relate to enhanced expression of phosphorylated ERK1/2 (pERK1/2). In this study, we investigated whether αB-crystallin expression is correlated to pERK1/2 expression in breast cancer. In a balanced tissue microarray the expression of αB-crystallin and pERK1/2 kinase were determined immunohistochemically, together with the triple-negativity and basal-like markers CK5/6 and SMA and the signaling molecules pAKT, pmTOR, EGFR, and IGF-1R. αB-crystallin expression significantly correlated with triple negativity and basal-like markers CK5/6 and SMA (Pearson Chi-square test p=0.004, p=0.001, and p<0.001, respectively). A significant correlation was also observed with pERK1/2 expression (p=0.002). siRNA-mediated knockdown of αB-crystallin in the triple-negative breast cell line MDA-MB468 did not show an effect on pERK1/2 expression levels, indicating that lowering the level of αB-crystallin does not reduce pERK1/2 expression. Our results confirm that αB-crystallin can be used as a biomarker for triple-negative and/or basal-like breast cancer. The expression of αB-crystallin correlates with pERK1/2 expression in breast cancer tissue suggesting that therapies targeting αB-crystallin might be considered for treatment of triple-negative or basal-like breast cancer.
αB-晶体蛋白被认为是三阴性和/或基底样乳腺癌的生物标志物。在正常乳腺细胞中,αB-晶体蛋白的过表达导致类肿瘤样变化,这可能与磷酸化 ERK1/2(pERK1/2)的表达增强有关。在这项研究中,我们研究了αB-晶体蛋白的表达是否与乳腺癌中 pERK1/2 的表达相关。在平衡的组织微阵列中,通过免疫组织化学测定αB-晶体蛋白和 pERK1/2 激酶的表达,以及三阴性和基底样标志物 CK5/6 和 SMA 以及信号分子 pAKT、pmTOR、EGFR 和 IGF-1R 的表达。αB-晶体蛋白的表达与三阴性和基底样标志物 CK5/6 和 SMA 显著相关(皮尔逊卡方检验 p=0.004、p=0.001 和 p<0.001)。与 pERK1/2 表达也存在显著相关性(p=0.002)。在三阴性乳腺癌细胞系 MDA-MB468 中,siRNA 介导的αB-晶体蛋白敲低并未显示对 pERK1/2 表达水平的影响,表明降低αB-晶体蛋白水平不会降低 pERK1/2 的表达。我们的结果证实,αB-晶体蛋白可用作三阴性和/或基底样乳腺癌的生物标志物。乳腺癌组织中αB-晶体蛋白的表达与 pERK1/2 的表达相关,这表明针对αB-晶体蛋白的治疗方法可能被考虑用于治疗三阴性或基底样乳腺癌。