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


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.


CONCLUSIONS
The impact of Hsp27, annexin III, annexin IV, Gp96 and TPT1 on the cellular response mechanism to HPV infection is presented and discussed.
Ciotti
Marco
M
Laboratory of Clinical Microbiology and Virology, University Hospital Tor Vergata, Rome, Italy. marco.ciotti@ptvonline.it
Marzano
Valeria
V
Giuliani
Laura
L
Nuccetelli
Marzia
M
D'Aguanno
Simona
S
Azzimonti
Barbara
B
Bernardini
Sergio
S
Perno
Carlo Federico
CF
Urbani
Andrea
A
Favalli
Cartesio
C
Federici
Giorgio
G
D015153:Blotting, Western; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D013058:Mass Spectrometry; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D050725:Papillomavirus E7 Proteins; D040901:Proteomics; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090324:Tumor Protein, Translationally-Controlled 1
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; C059731:oncogene protein E7, Human papillomavirus type 16