Expression of PRL-3 regulates proliferation and invasion of breast cancer cells in vitro

• Published in: Archives of gynecology and obstetrics Vol. 296; no. 6; pp. 1153 - 1160
• Main Authors: Radke, Isabel, Götte, Martin, Smollich, Martin, Scharle, Ninette, Kiesel, Ludwig, Wülfing, Pia
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2017; Springer Nature B.V
• Subjects: Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cadherins - genetics; Cadherins - metabolism; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cytoskeleton; Endocrinology; Female; Gene Expression; Gene Expression Regulation, Neoplastic - genetics; Gynecologic Oncology; Gynecology; Human Genetics; Humans; Lymphatic Metastasis; Matrix Metalloproteinase 9 - genetics; MCF-7 Cells; Medicine; Medicine & Public Health; Metastasis; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Proteins - genetics; Obstetrics/Perinatology/Midwifery; Protein Tyrosine Phosphatases - genetics; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Heparanase; Breast cancer; Proliferation; PRL-3; E-cadherin; Invasion
• ISSN: 0932-0067; 1432-0711
• DOI: 10.1007/s00404-017-4542-2

Purpose 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. Methods 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. Results 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. Conclusions 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.