Abstract
BackgroundPygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.MethodsIn the present study, the expression patterns of Pygo2 were evaluated by immunochemistry in 168 patients with non-small cell lung cancer (NSCLC). We used small interfering RNA (siRNA) to specifically silence Pygo2, and investigated its effect on cell growth by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis in human lung cancer cell lines.ResultsImmunohistochemical analysis showed low expression of Pygo2 in normal lung tissues and increased nuclear expression in lung cancer tissues, either with or without perinuclear expression. Abnormal Pygo2 expression was associated with poor differentiation and a high Tumor (T), Node (N) and Metastases (M) stage in NSCLC patients, and correlated with poor prognosis. Using MTT assay we observed that Pygo2 downregulation inhibited cell proliferation; in addition, flow cytometry analysis showed that Pygo2 knockdown induced apoptosis and increased numbers of G1-phase cells and a reduction in S-phase cells.ConclusionsWe therefore conclude that abnormal Pygo2 protein expression may be a marker for advanced NSCLC. Furthermore, Pygo2 knockdown suppresses cell growth.
Highlights
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex
Nuclear localization of Pygo2 in non-small cell lung cancer (NSCLC) To investigate the abnormalities of Pygo2 expression in NSCLC, we analyzed Pygo2 protein subcellular localization in 168 archived surgical tumor samples
Pygo2 overexpression correlates with some NSCLC clinicopathological factors and patient survival We investigated the associations between abnormal Pygo2 expression and clinicopathological factors
Summary
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex Despite this data, no clinical studies investigating Pygo expression in lung cancer have yet been reported. Due to the diverse roles of Pygo in cell regulation, disruption of Pygo function has been proposed as a strategy for targeting malignant cells [2,9]. In support of this hypothesis, studies have demonstrated that increased Pygo expression is required for proliferation of breast and SPC-A-1 and LTEP-a-2 lung cancer cell lines. We knocked down Pygo with small interfering RNA (siRNA) in human lung cancer cell lines and investigated its effect on cell proliferation
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