title: Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas.
abstract: We examined the expression of oncoprotein 18 (Op18) in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional PAGE analysis with confirmation by mass spectrometry and two-dimensional Western blot analysis. mRNA expression was examined using oligonucleotide microarrays, and the cellular localization of the Op18 protein was examined using immunohistochemical analysis of tissue microarrays. Three phosphorylated forms and one unphosphorylated form of the Op18 protein were identified and found to be overexpressed in lung adenocarcinomas as compared with normal lung. The percentage of phosphorylated to total Op18 protein isoforms increased from 3.2% in normal lung to 7.9% in lung tumors. Both the phosphorylated and unphosphorylated Op18 proteins were significantly increased in poorly differentiated tumors as compared with moderately or well differentiated lung adenocarcinomas (p<0.03), suggesting that up-regulated expression of Op18 reflects a poor differentiation status and higher cell proliferation rates. This was further verified in A549 and SKLU1 lung adenocarcinoma cell lines by examining Op18 levels and phosphorylation status following treatment that altered either cell proliferation or differentiation. The increased expression of Op18 protein was significantly correlated with its mRNA level indicating that increased transcription likely underlies elevated expression of Op18. The overexpression of Op18 proteins in poorly differentiated lung adenocarcinomas and the elevated expression of the phosphorylated forms of Op18 may offer a new target for drug- or gene-directed therapy and may have potential utility as a tumor marker.
authors.affiliation: Department of Surgery, The University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Tarek G
authors.initials: TG
authors.lastname: Gharib
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: Kerby A
authors.initials: KA
authors.lastname: Shedden
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: Mark D
authors.initials: MD
authors.lastname: Iannettoni
authors.forename: Mark B
authors.initials: MB
authors.lastname: Orringer
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D000595:Amino Acid Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D050777:Stathmin; D014158:Transcription, Genetic
chemical_list: D008868:Microtubule Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin