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Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer 被引量:31

Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer
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摘要 AIM: To investigate the expression of PTEN/MMAC1/TEP1 and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS: PTEN expression significantly decreased (t= 3.98, P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01) in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t=1.95, P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t= 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01), invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t=3.69, P<0.01), and there was a negative correlation betweenPTEN expression and MVD (γ=-0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04, P<0.01). MVD in VEGF-positive gaslyic cancer was significantly higher than that in VEGF-negative gastric cancer (t=4.62, P<0.01), and there was a positive correlation between VEGF expression of and MVD (y = 0.512, P<0.05). VEGF expression in PTEN-negative gaslyic cancer was significantly stronger than that in PTEN-positive gastric cancer (t=2.61, P<0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ=-0.403, P<0.05).CONCLUSION: Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN-related angiogenesis might be attributed to its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers. AIM:To investigate the expression of PTEN/MMAC_1/TEP_1 and vascular endothelial growth factor(VEGF),their roles in biologic behavior and angiogenesis and their association in gastric cancer. METHODS:Immunohistochemical staining was used to evaluate the expression of PTEN,VEGF and microvascular density(MVD)on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis(CSG).Expression of PTEN,VEGF and MVD were compared with clinicopathological features of gastric cancer.The relationship between expression of PTEN,VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS:PTEN expression significantly decreased(t=3.98, P<0.01)whereas both VEGF expression and MVD significant increased(t=4.29 and 4.41,respectively,both P<0.01) in gastric cancer group compared with CSG group.PTEN expression was significantly down-regulated(t=1.95, P<0.05)whereas VEGF expression(t=2.37,P<0.05)and MVD(t=3.28,P<0.01)was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer.PTEN expression in gastric cancer showed a negative association with lymph node metastasis(t=3.91,P<0.01), invasion depth(t=1.95,P<0.05)and age(t=4.69,P<0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer(t=3.69, P<0.01),and there was a negative correlation between PTEN expression and MVD(γ=-0.363,P<0.05).VEGF expression was positively associated with invasion depth (especially with serosa invasion,t=4.69,P<0.01),lymph node metastasis(t=2.31,P<0.05)and TNM stage(t=3.04, P<0.01).MVD in VEGF-positlve gastric cancer was significantly higher than that in VEGF-negative gastric cancer(t=4.62, P<0.01),and there was a positive correlation between VEGF expression of and MVD(γ=0.512,P<0.05).VEGF expression in PTEN-negative gastric cancer was significantly stronger than that in PTEN-positive gastric cancer(t=2.61, P<0.05),and there was a significantly negative correlation between the expression of VEGF and PTEN(γ=-0.403, P<0.O5). CONCLUSION:Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer.PTEN- related angiogenesis might be attributed to its up-regulation of VEGF expression.PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第21期3225-3229,共5页 世界胃肠病学杂志(英文版)
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  • 1Jaw-Yuan Wang,Tsung-Jen Huang,Fang-Ming Chen,Ming-Chia Hsieh,Shiu-Ru Lin,Ming-Feng Hou,Jan-Sing Hsieh.&nbsp&nbsp[J]. Virchows Archiv . 2003 (5)
  • 2Kiyoshi Sato,Gen Tamura,Takashi Tsuchiya,Yasushi Endoh,Ken Sakata,Teiichi Motoyama,Osamu Usuba,Wataru Kimura,Masanori Terashima,Satoshi Nishizuka,Tongtong Zou,Stephen J. Meltzer.Analysis of genetic and epigenetic alterations of the PTEN gene in gastric cancer[J].Virchows Archiv.2002(2)
  • 3Penelope Korkolopoulou,Anastasia E. Konstantinidou,Nikolaos Kavantzas,Efstratios Patsouris,Petros M. Pavlopoulos,Panagiota Christodoulou,Euphemia Thomas-Tsagli,Panagiotis Davaris.Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer[J].Virchows Archiv.2001(6)

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