<i>PLA2G7</i> associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial‐mesenchymal transition in cultured breast cancer cells

Abstract

Breast cancer is the leading cause of cancer-related deaths in women due to distinct cancer subtypes associated with early recurrence and aggressive metastatic progression. High lipoprotein-associated phospholipase A2 (<i>PLA2G7</i>) expression has previously been associated with aggressive disease and metastasis in prostate cancer. Here, we explore the expression pattern and functional role of <i>PLA2G7</i> in breast cancer. First, a bioinformatic analysis of genome-wide gene expression data from 970 breast samples was carried out to evaluate the expression pattern of <i>PLA2G7</i> mRNA in breast cancer. Second, the expression profile of <i>PLA2G7</i> was studied in 1042 breast cancer samples including 89 matched lymph node metastasis samples using immunohistochemistry. Third, the effect of <i>PLA2G7</i> silencing on genome-wide gene expression profile was studied and validated in cultured breast cancer cells expressing <i>PLA2G7</i> at high level. Last, the expression pattern of <i>PLA2G7</i> mRNA was investigated in 24 nonmalignant tissue samples and 65 primary and 7 metastatic tumour samples derived from various organs using qRT-PCR. The results from clinical breast cancer samples indicated that <i>PLA2G7</i> is overexpressed in a subset of breast cancer samples compared to its expression in benign breast tissue samples and that high <i>PLA2G7</i> expression associated with hormone receptor negativity as well as with poor prognosis in a subset of breast cancer samples. <i>In vitro</i> functional studies highlighted the putative role of <i>PLA2G7</i> in the regulation of epithelial-mesenchymal transition (EMT)-related signalling pathways, vimentin and E-cadherin protein expression as well as cell migration in cultured breast cancer cells. Furthermore, supporting the findings in breast and prostate cancer, high <i>PLA2G7</i> mRNA expression was associated with metastatic cancer in four additional organs of origin. In conclusion, our results indicate that <i>PLA2G7</i> is highly expressed in a subset of metastatic and aggressive breast cancers and in metastatic samples of various tissues of origin and promotes EMT and migration in cultured breast cancer cells.