Down-regulated expression of vascular endothelial growth factor-C inhibits the invasiveness of MCF-7 breast cancer cells

( views:, downloads: )
XIE Xiao-bin(Guangzhou Medical College)
LONG Jie(Guangzhou Medical College)
ZHANG Yan-qing(Guangzhou Medical College)
ZHANG Ya-jie(Guangzhou Medical College)
Journal Title:
Volume 15, Issue 06, 2009
Key Word:
Breast neoplasms;Vascular endothelial growth factor C;Matrix metalloproteinases; RNA interference; Invasion

Abstract: Objective To study whether down- regulation of vascular endothelial growth factor (VEGF)-C expression with RNA interference can inhibit the invasiveness of human MCF-7 breast cancer cells. Methods Recombinant vector (pSIREN-VEGF-C) was transfected into human breast cancer cell MCF -7 by liposome and positive transfected cell clones were screened with puromycin. Expression of VEGF-C in MCF- 7 cells after gene transfer was detected by real- time quantitative PCR and Western blot assay respectively. Invasiveness of transfected ceils were analyzed by Transwell filter. Expressions of MMP-2 and -9 mRNA were detected by semi-quantitative RT-PCR in transfected cells.Results The expressions of VEGF-C mRNA and proteins were reduced markedly compared with control group after transfection and the inhibition rate was 95% and 100% respectively (P<0.05).The invasiveness as reflected by number of Transwell filter penetrating MCF-7 cells declined evidently in those transfected by pSIREN-VEGF-C as compared to those without transfection (P<0.05).The expressions of MMP-2 and -9 mRNA in transfected cells were down-regulated significantly compared with control group and the inhibition rate was 55% and 75% respectively (P<0.05).Conclusion Down-regulating the expression of VEGF-C may significantly inhibit the invasiveness of human MCF-7 breast cancer cells.

  • [1]Smiqal C,Jemal A,Wrad E,et al.Trends in Breast cancer by race and ethnicity:update 2006.CA Cancer J Clin,2006,56:168-183.
  • [2]刘芳,张雅洁.VEGF-C及其受体Flt-4在乳腺癌转移中的作用.临床与实验病理学杂志,2003,19:252-254.
  • [3]Ueda M,Terai Y,Yamashita Y,et al.Correlation between vascular endothelial growth faetor-C expression and invasion phenotype in cervical carcinomas.Int J Cancer,2002,98:335-343.
  • [4]Ueda M,Hung YC,Terai Y,et al.Vascular endothelial growth factor-C expression and invasive phenotype in ovarian carcinomas.Clin Cancer Res,2005,11:3225-3232.
  • [5]谢晓斌,刘启才,张雅洁.抑制人血管内皮生长因子C表达的shRNA逆转录病毒表达载体的构建.广州医学院学报,2007,35:58-61.
  • [6]Ivan B,Sengül T,Igor G,et al.Expression of PEA3/E1AF/ETV4,an Ets-relatod transcription factor,in breast tumors:positive links to MMP2,NRG1 and CGB expression.J Carcinogenesis,2004,25:405-411.
  • [7]Lockwood CJ,Oner C,Uz YH,et al.Matrix metalloproteinase 9(MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells.Biol Reprod,2008,78:1064-1072.
  • [8]Tian X,Cong M,Zhou W,et al.Relationship between protein expression of VEGF-C,MMP-2 and lymph node metastasis in papillary thyroid cancer.J Int Med Res,2008,36:699-703.
  • [9]Achen MG,Stacker SA.Molecular control of lymphatic metastasis.Ann N Y Acad Sci,2008,1131:225-234.
  • [10]Lópoz de Cicco R,Watson JC,Bassi DE,et al.Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression.Clin Cancer Res,2004,10:4480-4488.
  • [11]Ricca A,Biroocio A,Del Bufalo D,et al.Bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCFT(ADR) bresst-cancer cells.Int J Cancer,2000,86:188-196.
  • [12]Dias S,Choy M,Alitalo K.Vascular endothelial growth factor(VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation,survival,and resistance to chemotherapy.Blood,2002,99:2179-2184.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615