The pro-angiogenic factors stimulated by human papillomavirus type 16 E6 and E7 protein in C33A and human fibroblasts

Oncol Rep. 2009 Jan;21(1):25-31.

Abstract

To investigate the pro-angiogenic factors stimulated by human papillomavirus type 16 E6 and E7 protein in C33A and human fibroblasts. HPV-16 E6 and E7 genes were transfected into C33A and HFB to detect the profiling of angiogenesis-associated factors with the TranSignal angiogenesis antibody array. The mRNA and protein levels of the cytokines were examined by traditional RT-PCR and Western blotting in both cell lines before and after transfection of HPV-16 E6 and E7. HPV-16 E6 and E7 genes were successfully transfected into C33A and HFB cells. On the sheet of antibody array, after transfection of HPV-16 E6 and E7, 6 other cytokines, Ang-1, FGFalpha, HGF, IL-6, IP-10 and PIGF besides VEGF, were detected at higher levels in C33A cells. Expression of 7 other cytokines besides IL-8, Ang-1, IL-1alpha, IL-1beta, HGF, IL-6, VEGF and PIGF increased in HFB cells. The common cytokines in both cell lines were Ang-1, HGF, PIGF and VEGF. The mRNA and protein levels of the four cytokines were verified to increase by traditional RT-PCR and Western blotting in both cell lines after transfection of HPV-16 E6 and E7. Multiple pro-angiogenic cytokines could be stimulated by HPV-16 E6 and E7 protein both in cervical cancer cell line and normal human diploid cells. Anti-angiogenesis therapy may be effective alone or in combination with biologic means aimed at E6 and E7 in the treatment of cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Blotting, Western
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Female
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / virology
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus E7 Proteins
  • Protein Array Analysis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / virology*

Substances

  • Angiogenesis Inducing Agents
  • Cytokines
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16