PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.
PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.
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DOI：
10.1371/journal.pone.0084472
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ataseven B
中科院分区：
文献类型：
--
作者：
Gärtner S;Gunesch A;Knyazeva T;Wolf P;Högel B;Eiermann W;Ullrich A;Knyazev P;Ataseven B
蛋白酪氨酸激酶 7 (PTK7) 在多种人类癌症中表达上调；然而，其在乳腺癌（BC）和淋巴结（LN）中的临床意义仍不清楚。为了研究PTK7在介导BC细胞运动和侵袭性中的功能，测定了BC细胞系中PTK7的表达。高侵袭性乳腺癌细胞中的 PTK7 信号传导受到显性失活 PTK7 突变体、针对 PTK7 胞外结构域的抗体和 PTK7 的 siRNA 敲低的抑制。这导致 BC 细胞的运动性和侵袭性降低。我们进一步通过 RT-PCR 检测了 128 例 BC 患者的 BC 和 LN 组织中 PTK7 的表达及其与 HER2、HER3、PAI1、MMP1、K19 和 CD44 等 BC 相关基因的相关性。 BC 细胞系和原发性肿瘤中的表达谱显示 PTK7 与 ER/PR/HER2 阴性（TNBC-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 分类为与原发性 BC 攻击行为相关的基因簇。此外，PTK7 表达在 BC 中的肿瘤大小（ANOVA，p = 0.033）和 LN 中的淋巴结受累（ANOVA，p = 0.007）方面显着不同。转移性 LN 中的 PTK7 表达与较短的 DFS 相关（Cox 回归，p = 0.041）。我们的观察证实了 PTK7 的转化潜力，及其参与 BC 细胞的运动和侵袭性。 PTK7 在 TNBC 细胞系中高表达。它代表了 BC 患者的一种新的预后标志物，具有潜在的治疗意义。
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.
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影响因子：
15.9
作者：
Jechlinger, Martin;Sommer, Andreas;Gruenert, Stefan
通讯作者：
Gruenert, Stefan
影响因子：
45.3
作者：
Endoh, H;Tomida, S;Mitsudomi, T
通讯作者：
Mitsudomi, T
影响因子：
56.9
作者：
Saha, S;Bardelli, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
DOI：
10.1016/j.bbrc.2008.04.168
发表时间：
2008-07-11
影响因子：
3.1
作者：
Shin, Won-Sik;Maeng, Yong-Sun;Lee, Seung-Taek
通讯作者：
Lee, Seung-Taek