Proteomic analysis of eIF-5A in lung adenocarcinomas.
We examined the eIF-5A protein expression in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis with identification by mass spectrometry and 2-D Western blots. The same tissue samples were examined for the eIF-5A mRNA expression using oligonucleotide microarrays, and the cellular localization of the eIF-5A protein was examined using immunohistochemical analysis on tissue arrays. Higher eIF-5A protein expression was present in tumors showing poor differentiation, 12/13(th) codon K-ras mutations, p53 nuclear accumulation, and tumors with positive lymphocytic response. The eIF-5A mRNA was also significantly increased in lung adenocarcinomas compared to normal lung, but the eIF-5A protein expression was not correlated to its mRNA levels indicating that the increase in the eIF-5A protein expression in lung tumors is post-transcriptionally/translationally/post-translationally regulated. Patients having a higher eIF-5A protein expression showed a relatively poorer survival suggesting the use of eIF-5A as prognostic marker in lung adenocarcinoma. Moreover, the investigation on agents that inhibit eIF-5A function is encouraged.
Chen
Guoan
G
Department of Surgery, The University of Michigan, Ann Arbor, MI 48109-086, USA.
Gharib
Tarek G
TG
Thomas
Dafydd G
DG
Huang
Chiang-Ching
CC
Misek
David E
DE
Kuick
Rork D
RD
Giordano
Thomas J
TJ
Iannettoni
Mark D
MD
Orringer
Mark B
MB
Hanash
Samir M
SM
Beer
David G
DG
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010448:Peptide Initiation Factors / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D016898:Interferon-alpha; D015850:Interleukin-6; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D000097574:Eukaryotic Translation Initiation Factor 5A