Abstract #3549: Alteration of 14-3-3 protein isoforms and annexin A5 expression in mouse lung tumors induced by the tobacco-specific nitrosamine NNK: potential clinical application in non^_small cell lung cancer (NSCLC) patients

Abstract

The heavy burden of lung cancer and the failure of standard approaches to reduce mortality direct our research toward the identification of lung cancer signature proteins and the development of novel chemopreventive agents; such proteins could be used as biomarkers for early detection of the disease and to monitor the efficacy of chemopreventive and therapeutic agents. Two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) and western immunoblotting were carried out on frozen mouse lungs (normal and tumor) from a previously conducted efficacy study with the chemopreventive organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) to identify and validate proteins that were modulated by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); three groups (4 lungs/group) were used in this study, vehicle-treated control, NNK-treated, and (NNK + p-XSC)-treated. In mouse lung tissue, we identified SEC14-like 3, dihydropyrimidinase-like 2, proteasome subunit \#945; type 5, annexin A5 (anxA5), 14-3-3 protein isoforms (\#949;, \#950;, \#952;, and \#963;), Rho GDP dissociation inhibitor (GDI) \#945;, myosin light polypeptide 6, tubulin-\#945;-1, vimentin, Atp5b protein, \#945;-1-antitrypsin, and Clara cell 10 kDa protein (CC10); some of these proteins are biologically relevant in the development of lung cancer. Those proteins (e.g. 14-3-3 protein isforms, anxA5) that were down-regulated in the NNK-treated group compared to the vehicle-treated control group were restored in the (NNK + p-XSC) group. To translate our preclinical findings to the clinic, we examined whether certain proteins identified in the NNK-A/J mouse model can be detected by immunoblot in human plasma from healthy subjects and NSCLC patients receiving chemotherapy. In human plasma from lung cancer patients, the expression levels of 14-3-3 \#963; and anxA5 were lower than those of healthy subjects. The expression levels of these two proteins appeared to increase following chemotherapy. Although these results are based on a limited number of samples, we propose that 14-3-3 \#963; and anxA5 proteins are potential biomarkers for early detection of the disease and to monitor the efficacy of chemopreventive and chemotherapeutic agents. Support: NCI PO1 70972

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3549.