[Show abstract][Hide abstract] ABSTRACT: The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.
PLoS ONE 01/2013; 8(4):e60821. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the role of β-catenin in pathogenesis of nasopharyngeal carcinoma (NPC).
Cellular proliferation, apoptosis, matrix penetration assay, and western blotting were employed to determine cell biological changes in NPC cell lines transfected with β-catenin siRNA. Immunohistochemistry staining was used to detect β-catenin and Ki-67 expression in NPC tissue.
β-Catenin was upregulated in NPC cell lines and tissues compared with chronic nasopharyngitis tissue. β-Catenin knockdown dramatically inhibited cellular growth, migration and invasion, but induced apoptosis of NPC cells. Further study showed that downstream genes of β-catenin signaling pathway including cyclin D1, c-Myc, MMP2 and MMP9 expression were suppressed in NPC cell lines transfected with β-catenin siRNA.
Targeting β-catenin signaling pathway may be a noval strategy for NPC therapy.
[Show abstract][Hide abstract] ABSTRACT: To investigate retinoid X receptor alpha (RXRα) and β-catenin expression and their relationship with the clinicopathological features of colorectal carcinoma (CRC). Real-time PCR and western blot analyses revealed that β-catenin and RXRα expression at both mRNA and protein levels in four pairs of fresh CRC and adjacent non-tumour tissues (ANT) dramatically was increased and decreased in CRC compared with ANT, respectively. Furthermore, RXRα expression at both mRNA and protein levels was downregulated in higher histological grade CRC. Immunohistochemistry staining in 120 cases of CRC and 60 cases of lymph node metastatic carcinoma of CRC showed that RXRα expression was significantly suppressed in CRC compared with ANT (P<0.001) and low expression of RXRα in CRC was significantly associated with histological grade (P<0.001), TNM stage (P=0.022) and N classification (P=0.002). The aberrant (accumulated cytoplasm or/and nuclei) expression of β-catenin was higher in CRC than that in ANT (P<0.001) and associated with histological grade (P=0.001) and N classification (P=0.002). Moreover, there was a close relationship between low RXRα expression and aberrant β-catenin expression in CRC (P=0.032). Taken together with our previous study, aberrant β-catenin expression upregulated by suppression of RXRα may play a crucial role in pathogenesis and progression of CRC.
European journal of cancer (Oxford, England: 1990) 05/2011; 47(13):2060-7. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper aimed to study whether Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) regulates β-catenin signaling pathway in nasopharyngeal carcinoma (NPC). Western blotting, immunofluorescence, luciferase reporter assay, co-immunoprecipitation assay, and immunohistochemistry staining were used. LMP1 increased β-catenin transcriptional activity in NPC cell lines. The upregulation of β-catenin transcriptional activity induced by LMP1 was much higher in poorly differentiated NPC cell line CNE2 than that in well-differentiated NPC cell line CNE1. Immunofluorescence staining and Western blotting also showed that LMP1 increased nuclear β-catenin accumulation in NPC cell lines. Moreover, LMP1 expression was closely related to abnormal β-catenin expression in NPC tissues by immunohistochemistry. LMP1 may be involved in nasopharyngeal carcinogenesis via β-catenin signaling pathway.