Antibody-based proteomics for esophageal cancer: Identification of proteins in the nuclear factor-kappaB pathway and mitotic checkpoint.
To identify the molecular background of esophageal cancer, we conducted a proteomics study using an antibody microarray consisting of 725 antibodies and surgical specimens from three cases. The microarray analysis identified 24 proteins with aberrant expression in esophageal cancer compared with the corresponding normal mucosa. The overexpression of 14 of the 24 proteins was validated by western blotting analysis of the same samples. These 14 proteins were examined by immunohistochemistry, in which nine proteins showed consistent results with those obtained by western blotting. Among the nine proteins, seven were localized in tumor cells, and two in infiltrating cells. The former included proteins associated with mitotic checkpoint control and the nuclear factor (NF)-kappaB pathway. Although mitotic checkpoint gene products (budding uninhibited by benzidazoles 1 homolog beta (BubR1) and mitotic arrest deficient-like 1 (Mad2)) have previously been reported to be involved in esophageal cancer, the association of NF-kappaB-activating kinase, caspase 10, and activator protein-1 with esophageal cancer has not been previously reported. These proteins play a key role in the NF-kappaB pathway, and NF-kappaB is a signal transduction factor that has emerged as an important modulator of altered gene programs and malignant phenotype in the development of cancer. The association of these proteins with esophageal cancer may indicate that mitotic checkpoint gene products and NF-kappaB play an important part in the carcinogenesis of esophageal cancer.
Uemura
Norihisa
N
Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Nakanishi
Yukihiro
Y
Kato
Hoichi
H
Nagino
Masato
M
Hirohashi
Setsuo
S
Kondo
Tadashi
T
D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D053455:Caspase 10 / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000737:chemistry*; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000032:analysis
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D053455:Caspase 10