Radke Isabel, Götte Martin, Smollich Martin, Scharle Ninette, Kiesel Ludwig, Wülfing Pia
Department of Gynecology and Obstetrics, University of Münster, Albert-Schweitzer-Campus 1 A1, 48149, Munster, Germany.
Arch Gynecol Obstet. 2017 Dec;296(6):1153-1160. doi: 10.1007/s00404-017-4542-2. Epub 2017 Oct 4.
The protein tyrosine phosphatase PRL-3 plays an important role in cancer cell migration, invasion and metastasis. In breast cancer, PRL-3 is overexpressed in 70-75% of tumors and even more frequently in lymph node metastases. Moreover, PRL-3 overexpression in breast cancer is associated with an adverse disease outcome. Aim of this study was to determine the role of PRL-3 in breast cancer cell proliferation, migration and invasion in vitro.
PRL-3 mRNA expression was evaluated in 6 breast cancer cell lines by quantitative real-time PCR. To investigate the effect of PRL-3 expression in breast cancer cells in vitro we both up- and downregulated PRL-3 expression in breast cancer cells and performed in vitro wound repair cell motility assays and invasion assays. The influence of PRL-3 knockdown in MCF-7 cells on the expression of several gene products involved in cell invasion and cytoskeletal function was evaluated with real-time PCR.
PRL-3 mRNA expression was demonstrated in all breast cancer cell lines evaluated. Knockdown of PRL-3 in MCF-7 cells resulted in decreased proliferation, wound healing and invasion. PRL-3 knockdown in MCF-7 cells resulted in a significant reduction of heparanase, MMP-9, actin gamma-2 and Myosin 9 expression, and significant elevation of E-cadherin.
We conclude that PRL-3 is an important regulatory factor for breast cancer cell proliferation and invasion. Loss of PRL-3 function induces an antimetastatic gene expression profile in breast cancer cells. Due to its role in tumor growth and metastasis, PRL-3 emerges as a new therapeutic target in breast cancer therapy.
蛋白酪氨酸磷酸酶PRL-3在癌细胞迁移、侵袭和转移中起重要作用。在乳腺癌中，70%-75%的肿瘤中PRL-3过表达，在淋巴结转移中更为常见。此外，乳腺癌中PRL-3过表达与不良疾病预后相关。本研究的目的是确定PRL-3在体外乳腺癌细胞增殖、迁移和侵袭中的作用。
通过定量实时PCR评估6种乳腺癌细胞系中PRL-3 mRNA的表达。为了研究PRL-3表达对体外乳腺癌细胞的影响，我们上调和下调了乳腺癌细胞中PRL-3的表达，并进行了体外伤口修复细胞运动分析和侵袭分析。用实时PCR评估MCF-7细胞中PRL-3基因敲低对几种参与细胞侵袭和细胞骨架功能的基因产物表达的影响。
在所评估的所有乳腺癌细胞系中均证实了PRL-3 mRNA的表达。MCF-7细胞中PRL-3基因敲低导致增殖、伤口愈合和侵袭减少。MCF-7细胞中PRL-3基因敲低导致乙酰肝素酶、基质金属蛋白酶-9、肌动蛋白γ-2和肌球蛋白9表达显著降低，E-钙黏蛋白显著升高。
我们得出结论，PRL-3是乳腺癌细胞增殖和侵袭的重要调节因子。PRL-3功能丧失诱导乳腺癌细胞中抗转移基因表达谱。由于其在肿瘤生长和转移中的作用，PRL-3成为乳腺癌治疗中的一个新的治疗靶点。
