Tumor suppressor gene 14-3-3sigma is down-regulated whereas the proto-oncogene translation elongation factor 1delta is up-regulated in non-small cell lung cancers as identified by proteomic profiling.
Lung cancer, a leading cause of cancer deaths, consists of two major groups: small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC) with the NSCLC accounting for approximately 75% cases of lung cancers. It has been suggested that molecular changes including overexpression of oncogenes and decreased expression of tumor suppressor genes are responsible for lung carcinogenesis. In this study, we analyzed protein profiles of four different human NSCLC cell lines compared with normal human bronchial epithelial cells using two-dimensional PAGE and MALDI-TOF mass spectrometry. We identified 12 protein spots with different expressions between the normal and cancer cells. Of these proteins, vimentin, cytokeratin 8, YB-1, PCNA, Nm23, hnRNP A2/B1, and HSP90beta were known to be up-regulated in lung cancers, which is consistent with the current study. We also found that the expression of M-type pyruvate kinase is altered in NSCLC likely due to changes in translational control and/or differential phosphorylation of the protein. Interestingly, the expression of the tumor suppressor gene 14-3-3sigma is down-regulated while that of the proto-oncogene TEF1delta is up-regulated in NSCLC cells. On the basis of these observations and previous studies, we propose that the altered expression of 14-3-3sigma and TEF1delta may be involved in lung carcinogenesis.
Liu
Yang
Y
Department of Pharmacology and Toxicology, Walther Oncology Center/Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Chen
Qun
Q
Zhang
Jian-Ting
JT
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D005092:Exonucleases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D000090063:Proto-Oncogene Mas; D011770:Pyruvate Kinase / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D020648:Peptide Elongation Factor 1; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011770:Pyruvate Kinase; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human