Jingjing Ma1,2,3, Xufeng Guo4,2, Jixiang Zhang1,2,3, Dandan Wu1, Xue Hu1, Jiao Li1, Qingzhi Lan1, Ya Liu1, Weiguo Dong5. 1. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, Hubei Province, People's Republic of China. 2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, People's Republic of China. 3. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China. 4. Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China. 5. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, Hubei Province, People's Republic of China. dongweiguo@whu.edu.cn.
Abstract
BACKGROUND: Abnormality of PTEN gene and Wnt/β-catenin signaling have been strongly implicated in various malignant cancers. Recently, it has been noted that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and Wnt/β-catenin, which plays a key role in the development of cancers. However, few related studies on gastric cancer are available. AIM: We examined the expression of PTEN and β-catenin in gastric cancer tissues and detected whether down-regulation of PTEN promotes the migration and invasion in gastric cancer cells along with its underlying mechanism. MATERIALS AND METHODS: Immunocytochemistry, a wound healing assay, a Matrigel invasion assay, an immunofluorescence staining were performed to detect expression of PTEN and β-catenin in gastric cancer and adjacent normal tissues, cell migration, cell invasion, and the effects of PTEN knockdown on β-catenin in cells, respectively. Further, MMP-2 and MMP-9 activities were analyzed by zymography assay. The changes in related proteins were further quantified by western blotting. RESULTS: Low expression of PTEN was found in majority of gastric cancer tissues, which showed significant associations with differentiation grade in gastric cancer patients. Further, a negative correlation was revealed between PTEN and β-catenin protein expression in gastric cancer tissues (r = - 0.546, P < 0.01). Additionally, PTEN knockdown promoted the migration and invasion of cells and caused an obvious increase in p-AKT, p-GSK-3β, β-catenin, E-cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells. CONCLUSION: Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.
BACKGROUND: Abnormality of PTEN gene and Wnt/β-catenin signaling have been strongly implicated in various malignant cancers. Recently, it has been noted that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and Wnt/β-catenin, which plays a key role in the development of cancers. However, few related studies on gastric cancer are available. AIM: We examined the expression of PTEN and β-catenin in gastric cancer tissues and detected whether down-regulation of PTEN promotes the migration and invasion in gastric cancer cells along with its underlying mechanism. MATERIALS AND METHODS: Immunocytochemistry, a wound healing assay, a Matrigel invasion assay, an immunofluorescence staining were performed to detect expression of PTEN and β-catenin in gastric cancer and adjacent normal tissues, cell migration, cell invasion, and the effects of PTEN knockdown on β-catenin in cells, respectively. Further, MMP-2 and MMP-9 activities were analyzed by zymography assay. The changes in related proteins were further quantified by western blotting. RESULTS: Low expression of PTEN was found in majority of gastric cancer tissues, which showed significant associations with differentiation grade in gastric cancerpatients. Further, a negative correlation was revealed between PTEN and β-catenin protein expression in gastric cancer tissues (r = - 0.546, P < 0.01). Additionally, PTEN knockdown promoted the migration and invasion of cells and caused an obvious increase in p-AKT, p-GSK-3β, β-catenin, E-cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells. CONCLUSION: Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.
Authors: P A Steck; M A Pershouse; S A Jasser; W K Yung; H Lin; A H Ligon; L A Langford; M L Baumgard; T Hattier; T Davis; C Frye; R Hu; B Swedlund; D H Teng; S V Tavtigian Journal: Nat Genet Date: 1997-04 Impact factor: 38.330
Authors: L Davidson; H Maccario; N M Perera; X Yang; L Spinelli; P Tibarewal; B Glancy; A Gray; C J Weijer; C P Downes; N R Leslie Journal: Oncogene Date: 2009-11-16 Impact factor: 9.867