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

Abstract

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 twodimensional 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 NNKtreated 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, dihydropyrimidinaselike 2, proteasome subunit α type 5, annexin A5, 14-3-3 protein isoforms (θ, ε, σ, and ζ), Rho GDP dissociation inhibitor α, myosin light polypeptide 6, tubulin-α-1, vimentin, Atp5b protein, α-1-antitrypsin, and Clara cell 10 kDa protein (CC10). Among those proteins, we demonstrated for the first time that 14-3-3 isoforms (θ, ε, and σ) 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.

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

“…Exposure to tobacco smoke and lung carcinogens have been associated with reduced levels of clara cell protein 10 (CC10) and numerous studies have indicated that decreased levels of CC10 exist in both bronchoalveolar lavage fluid (BALF) and serum of smokers and lung cancer patients compared to healthy nonsmokers [38,39]. Chin et al showed that the levels of CC10 in plasma and BALF could be restored following smoking cessation, suggesting that the damage caused by tobacco smoke could be repaired [40].…”

Targeting 14-3-3zeta in cancer therapy

“…Sometimes, cytoplasmic and nuclear expression is observed even in the same tissue. 19 14-3-3zeta-positive expression occurs in the lung cancer, [25][26][27][28] liver cancer, 21 uterus, breast carcinoma, 14 stomach cancer, 29 head and neck squamous cell carcinoma 15 and so on. In addition, 14-3-3zeta protein expression is elevated in the breast cancer, 14 36 which shows 14-3-3zeta overexpression also occurred in cervical, ovarian, skin, pancreatic, prostate and urothelial tumors.…”

Early Second-Trimester Peptidomic Identification of Serum Peptides for Potential Prediction of Gestational Diabetes Mellitus

“…The threshold of significance was defined by the P-value and FDR. To further explore the significance of differentially-expressed peptides and their precursor proteins, they were imported into the Ingenuity Pathway Analysis (IPA) Software v7.1 (Ingenuity Systems, Mountain View, CA) for pathway analysis as described previously [15]. This software can also be used for biochemical, biologic, and molecular functions.…”