Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Institute for medical statistics and epidemiology, Klinikum rechts der Isar, Technical University, Munich, Germany.
PLoS One. 2014 Jan 7;9(1):e84472. doi: 10.1371/journal.pone.0084472. eCollection 2014.
Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.
蛋白酪氨酸激酶 7(PTK7)在多种人类癌症中上调;然而,其在乳腺癌(BC)和淋巴结(LN)中的临床意义尚不清楚。为了研究 PTK7 在介导 BC 细胞迁移和侵袭性中的功能,测定了 BC 细胞系中 PTK7 的表达。通过显性失活 PTK7 突变体、针对 PTK7 细胞外结构域的抗体和 PTK7 的 siRNA 敲低抑制高度侵袭性乳腺癌细胞中的 PTK7 信号,导致 BC 细胞迁移和侵袭性降低。我们进一步通过 RT-PCR 检测了 128 例 BC 患者的 BC 和 LN 组织中的 PTK7 表达,并与其相关基因(如 HER2、HER3、PAI1、MMP1、K19 和 CD44)的相关性进行了分析。BC 细胞系和原发肿瘤的表达谱分析表明,PTK7 与 ER/PR/HER2 阴性(三阴性 BC)癌症相关。Oncomine 数据分析证实了这一观察结果,并将 PTK7 归类为与原发性 BC 侵袭性行为相关基因的聚类。此外,PTK7 的表达与 BC 肿瘤大小(ANOVA,p=0.033)和 LN 淋巴结受累(ANOVA,p=0.007)显著相关。转移性 LN 中 PTK7 的表达与 DFS 较短(Cox 回归,p=0.041)相关。我们的观察结果证实了 PTK7 的转化潜力及其在 BC 细胞迁移和侵袭性中的作用。PTK7 在三阴性 BC 细胞系中高表达。它是 BC 患者的一种新的预后标志物,具有潜在的治疗意义。