Proteomic investigation in A549 lung cell line stably infected by HPV16E6/E7 oncogenes

Respiration. 2009;77(4):427-39. doi: 10.1159/000176209. Epub 2008 Nov 20.

Abstract

Background: Data have accumulated implicating the involvement of oncogenic human papillomaviruses (HPVs) in bronchial carcinogenesis. We recently described the presence of oncogenic HPV transcripts in non-small cell lung cancers.

Objective: To investigate the role of oncogenic HPVs in lung carcinogenesis.

Material and methods: The lung cell line A549 stably infected with HPV16E6, HPV16E7 and HPVE6/E7 constructs was used to investigate the protein profile changes associated with the expression of these oncogenes. Replicated two-dimensional gel electrophoresis gels from uninfected and stably HPV16E6-, E7-, and E6/E7-infected A549 cells were compared for changes in protein profile. Protein identification was achieved by peptide mass fingerprinting by MALDI-TOF-MS and nLC-ESI-Q-TOF-MS/MS peptide ladder sequencing.

Results: We identified 17 different polypeptides whose average normalized spot intensity was statistically significant (p < 0.05) and differed by 2-fold. Relationships between differentially expressed proteins and the HPV-induced infection mechanism have been clustered by knowledge-base database functional association network analysis.

Conclusion: The impact of Hsp27, annexin III, annexin IV, Gp96 and TPT1 on the cellular response mechanism to HPV infection is presented and discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / metabolism
  • Mass Spectrometry
  • Oncogene Proteins, Viral / genetics*
  • Oncogenes
  • Papillomavirus E7 Proteins
  • Proteomics*
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Protein, Translationally-Controlled 1

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • TPT1 protein, human
  • Tumor Protein, Translationally-Controlled 1
  • oncogene protein E7, Human papillomavirus type 16