Down-regulation of 14-3-3 isoforms and annexin A5 proteins in lung adenocarcinoma induced by the tobacco-specific nitrosamine NNK in the A/J mouse revealed by proteomic analysis.
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen in the A/J mouse model. Here we identified and validated, using two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry and immunoblotting, proteins that are differentially expressed in the lungs of mice treated with NNK versus vehicle control treatment. We also determined whether protein levels in the lungs of NNK-treated mice could be further modulated by the chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC). The proteins identified in this study are SEC14-like 3, dihydropyrimidinase-like 2, proteasome subunit alpha type 5, annexin A5, 14-3-3 protein isoforms (theta, epsilon, sigma, and zeta), Rho GDP dissociation inhibitor alpha, myosin light polypeptide 6, tubulin-alpha-1, vimentin, Atp5b protein, alpha-1-antitrypsin, and Clara cell 10 kDa protein (CC10). Among those proteins, we demonstrated for the first time that 14-3-3 isoforms (theta, epsilon, and sigma) and annexin A5 were significantly down-regulated in mouse lung adenocarcinoma induced by NNK and were recovered by p-XSC. These proteins are involved in a variety of biological functions that are critical in lung carcinogenesis. Identification of these proteins in surrogate tissue in future studies would be highly useful in early detection of lung adenocarcinoma and clinical chemoprevention trials.
Bortner
James D
JD
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
Das
Arunangshu
A
Umstead
Todd M
TM
Freeman
Williard M
WM
Somiari
Richard
R
Aliaga
Cesar
C
Phelps
David S
DS
El-Bayoumy
Karam
K
D048948:14-3-3 Proteins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D002273:Carcinogens; D016000:Cluster Analysis; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006651:Histocytochemistry; D015151:Immunoblotting; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines; D016566:Organoselenium Compounds; D025941:Protein Interaction Mapping; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D048948:14-3-3 Proteins; D017304:Annexin A5; D002273:Carcinogens; D009602:Nitrosamines; D016566:Organoselenium Compounds; D020033:Protein Isoforms; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C074153:1,4-phenylenebis(methylene)selenocyanate