7039

TGFA

AIMS: Determination of prognostic parameters that are predictive of survival of gastric cancer (GC) may allow better identification of patients who could benefit from current chemotherapy regimens. To assess the correlation between tumour progression and epithelial-mesenchymal transition (EMT), we assayed the expression levels of selected molecules involved in EMT [CD44, transforming growth factor (TGF)-alpha, cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-7, MMP-9 and C-X-C chemokine receptor (CXCR4)], and correlated these with overall patient survival (OS) and disease stage. METHODS AND RESULTS: Medical records and pathological biopsy results of 137 patients with GC were evaluated retrospectively. Spearman's correlation analysis showed that expression of CXCR4 was correlated significantly with the expression of all other proteins studied. In contrast, COX-2 expression correlated significantly with the expression of only MMP-7 (P = 0.011), MMP-9 (P = 0.015) and CXCR4 (P = 0.013). We observed significant negative correlations between OS and the expression of TGF-alpha (P = 0.017), COX-2 (P < 0.001), CXCR4 (P = 0.010), MMP-7 (P = 0.020) and MMP-9 (P = 0.015). On multivariate analysis, only COX-2 was an independent prognostic factor for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI): 1.43-9.75; P = 0.002). CONCLUSIONS: COX-2, TGF-alpha, MMP-7, MMP-9 and CXCR4 are associated with poor OS in gastric cancer.CI - (c) 2012 Blackwell Publishing Ltd.

Transforming growth factor-alpha (TGF-alpha) is upregulated in advanced stages of prostate cancer and strongly correlated with metastasis. However, the effect of TGF-alpha on epithelial-mesenchymal transition (EMT) in prostate cancer and the underlying mechanisms remain unclear. Recently, microRNAs have emerged as new regulators of EMT. This study found that treatment of DU145 cells with TGF-alpha suppressed the expression of epithelial marker E-cadherin and increased the expression of mesenchymal marker Vimentin as well as changed the cell morphology from cobblestone shape to spindle shape. The level of miR-124 was downregulated by TGF-alpha in several different cancer cell lines. Enforced expression of miR-124 abolished TGF-alpha-induced EMT. Slug was proven to be a target of miR-124 and mediated the inhibitory effect of miR-124 on TGF-alpha-induced EMT. Furthermore, overexpression of miR-124 reduced the migratory and invasive capacity of TGF-alpha-treated DU145 cells. In conclusion, our findings suggest that miR-124 inhibits TGF-alpha-induced EMT in DU145 cells by targeting Slug. Thus, miR-124 may be a potential target for prostate cancer therapeutic intervention.

Colon cancer is one of the most common cancers in the developed countries. The association between transforming growth factor TGFalpha and human cancer incidence has been suggested, yet, the regulatory roles of TGFalpha and the molecular mechanisms remain unknown, especially in colon cancer. We aim to investigate the functional regulations of TGFalpha in colon cancer progression. Two colon cancer cell lines were applied, and plasmid overexpression and siRNA-mediated depletion techniques were used to verify the role of TGFalpha in colon cancer. Cell proliferation was analyzed by MTS assay and colony formation assay, and western blot assay was used to examine protein expression. Migration, invasion, and reporter assays were also carried out to study the regulations of TGFalpha in colon cancer. Our results evidenced that expression of TGFalpha facilitates short-term and long-term proliferations of colon cancer cells. Moreover, TGFalpha was suggested as a migration-and-invasion promoting factor of colon cancer. Finally, our data indicated that TGFalpha modulates epithelial-mesenchymal transition (EMT) markers and NFkappaB signaling pathway in colon cancer cells. We provide the first time evidence of the promoting role TGFalpha plays in colon cancer tumorigenesis with proposed regulatory mechanisms involving EMT alteration and NFkappaB signaling pathway.CI - Copyright (c) 2018 Elsevier Inc. All rights reserved.