Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas.

Guoan Chen, Hong Wang, Tarek G. Gharib, Chiang Ching Huang, Dafydd G. Thomas, Kerby A. Shedden, Rork Kuick, Jeremy M.G. Taylor, Sharon L.R. Kardia, David E. Misek, Thomas J. Giordano, Mark D. Iannettoni, Mark B. Orringer, Samir M. Hanash, David G. Beer

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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.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalMolecular & cellular proteomics : MCP
Volume2
Issue number2
DOIs
StatePublished - Feb 2003

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Stathmin
Lung
Cell proliferation
Microarrays
Proteins
Tumors
Adenocarcinoma of lung
Cell Proliferation
Tissue Array Analysis
Messenger RNA
Phosphorylation
Transcription
Tumor Biomarkers
Oligonucleotide Array Sequence Analysis
Oligonucleotides
Genetic Therapy
Mass spectrometry
Cell Differentiation
Mass Spectrometry
Neoplasms

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

Chen, G., Wang, H., Gharib, T. G., Huang, C. C., Thomas, D. G., Shedden, K. A., ... Beer, D. G. (2003). Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. Molecular & cellular proteomics : MCP, 2(2), 107-116. https://doi.org/10.1074/mcp.M200055-MCP200

Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. / Chen, Guoan; Wang, Hong; Gharib, Tarek G.; Huang, Chiang Ching; Thomas, Dafydd G.; Shedden, Kerby A.; Kuick, Rork; Taylor, Jeremy M.G.; Kardia, Sharon L.R.; Misek, David E.; Giordano, Thomas J.; Iannettoni, Mark D.; Orringer, Mark B.; Hanash, Samir M.; Beer, David G.

In: Molecular & cellular proteomics : MCP, Vol. 2, No. 2, 02.2003, p. 107-116.

Research output: Contribution to journalArticle

Chen, G, Wang, H, Gharib, TG, Huang, CC, Thomas, DG, Shedden, KA, Kuick, R, Taylor, JMG, Kardia, SLR, Misek, DE, Giordano, TJ, Iannettoni, MD, Orringer, MB, Hanash, SM & Beer, DG 2003, 'Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas.', Molecular & cellular proteomics : MCP, vol. 2, no. 2, pp. 107-116. https://doi.org/10.1074/mcp.M200055-MCP200
Chen, Guoan ; Wang, Hong ; Gharib, Tarek G. ; Huang, Chiang Ching ; Thomas, Dafydd G. ; Shedden, Kerby A. ; Kuick, Rork ; Taylor, Jeremy M.G. ; Kardia, Sharon L.R. ; Misek, David E. ; Giordano, Thomas J. ; Iannettoni, Mark D. ; Orringer, Mark B. ; Hanash, Samir M. ; Beer, David G. / Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. In: Molecular & cellular proteomics : MCP. 2003 ; Vol. 2, No. 2. pp. 107-116.
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AU - Thomas, Dafydd G.

AU - Shedden, Kerby A.

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AU - Giordano, Thomas J.

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