Alterations in Barrett's-related adenocarcinomas: A proteomic approach

Dunfa Peng, Essam A. Sheta, Steven M. Powell, Christopher A. Moskaluk, Kay Washington, Ira L. Goldknopf, Wael El-Rifai

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In this study, we applied high-resolution, two-dimensional, gel electrophoresis and matrix-assisted laser desorption/ionization, time-of-flight and tandem mass spectrometry analysis (MALDI TOF MS) to identify novel proteins that are involved in Barrett's tumorigenesis. We analyzed 12 primary tissue samples that included 8 Barrett's-related adenocarcinomas (BA) and 4 normal mucosae samples. Twenty-three spots were consistently altered (≥2-fold) in at least half of the tumors when compared with all normal samples and thus subjected to further analysis. The MALDI TOF MS analysis demonstrated biologically interesting upregulated proteins such as ErbB3, Dr5 and Cyclin D1 as well as several members of the zinc finger proteins (Znf146, Znf212 and Znf363). Examples of downregulated proteins included Lgi1 and Klf6. We selected four proteins (ErbB3, Dr5, Znf146 and Lgi1) that are novel for BAs for validation using quantitative real-time reverse-transcription PCR on 39 BA tissue samples when compared with normal samples. We demonstrated mRNA upregulation of ERBB3 (51.3%), DR5 (41%) and ZNF146 (30.7%) and downregulation of LGI1 (100%) in BA. We have further validated the protein overexpression of ErbB3, Dr5 and Znf146, using immunohistochemical (IHC) analysis on a tissue microarray that contained 75 BAs and normal gastric and esophageal mucosae samples. BA tissue samples demonstrated overexpression of ErbB3 (42%), Dr5 (90%) and Znf146 (30%) when compared with normal tissues. In conclusion, we have identified and validated several novel proteins that are involved in Barrett's carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1303-1310
Number of pages8
JournalInternational Journal of Cancer
Volume122
Issue number6
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Fingerprint

Proteomics
Adenocarcinoma
Proteins
Tandem Mass Spectrometry
Carcinogenesis
Lasers
Down-Regulation
Cyclin D1
Zinc Fingers
Electrophoresis, Gel, Two-Dimensional
Gastric Mucosa
Reverse Transcription
Mucous Membrane
Up-Regulation
Polymerase Chain Reaction
Messenger RNA
Neoplasms

Keywords

  • Barrett's
  • Cancer
  • DR5
  • ErbB3
  • LGI1
  • Proteomics
  • Zinc finger proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peng, D., Sheta, E. A., Powell, S. M., Moskaluk, C. A., Washington, K., Goldknopf, I. L., & El-Rifai, W. (2008). Alterations in Barrett's-related adenocarcinomas: A proteomic approach. International Journal of Cancer, 122(6), 1303-1310. https://doi.org/10.1002/ijc.23258

Alterations in Barrett's-related adenocarcinomas : A proteomic approach. / Peng, Dunfa; Sheta, Essam A.; Powell, Steven M.; Moskaluk, Christopher A.; Washington, Kay; Goldknopf, Ira L.; El-Rifai, Wael.

In: International Journal of Cancer, Vol. 122, No. 6, 15.03.2008, p. 1303-1310.

Research output: Contribution to journalArticle

Peng, D, Sheta, EA, Powell, SM, Moskaluk, CA, Washington, K, Goldknopf, IL & El-Rifai, W 2008, 'Alterations in Barrett's-related adenocarcinomas: A proteomic approach', International Journal of Cancer, vol. 122, no. 6, pp. 1303-1310. https://doi.org/10.1002/ijc.23258
Peng D, Sheta EA, Powell SM, Moskaluk CA, Washington K, Goldknopf IL et al. Alterations in Barrett's-related adenocarcinomas: A proteomic approach. International Journal of Cancer. 2008 Mar 15;122(6):1303-1310. https://doi.org/10.1002/ijc.23258
Peng, Dunfa ; Sheta, Essam A. ; Powell, Steven M. ; Moskaluk, Christopher A. ; Washington, Kay ; Goldknopf, Ira L. ; El-Rifai, Wael. / Alterations in Barrett's-related adenocarcinomas : A proteomic approach. In: International Journal of Cancer. 2008 ; Vol. 122, No. 6. pp. 1303-1310.
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abstract = "In this study, we applied high-resolution, two-dimensional, gel electrophoresis and matrix-assisted laser desorption/ionization, time-of-flight and tandem mass spectrometry analysis (MALDI TOF MS) to identify novel proteins that are involved in Barrett's tumorigenesis. We analyzed 12 primary tissue samples that included 8 Barrett's-related adenocarcinomas (BA) and 4 normal mucosae samples. Twenty-three spots were consistently altered (≥2-fold) in at least half of the tumors when compared with all normal samples and thus subjected to further analysis. The MALDI TOF MS analysis demonstrated biologically interesting upregulated proteins such as ErbB3, Dr5 and Cyclin D1 as well as several members of the zinc finger proteins (Znf146, Znf212 and Znf363). Examples of downregulated proteins included Lgi1 and Klf6. We selected four proteins (ErbB3, Dr5, Znf146 and Lgi1) that are novel for BAs for validation using quantitative real-time reverse-transcription PCR on 39 BA tissue samples when compared with normal samples. We demonstrated mRNA upregulation of ERBB3 (51.3{\%}), DR5 (41{\%}) and ZNF146 (30.7{\%}) and downregulation of LGI1 (100{\%}) in BA. We have further validated the protein overexpression of ErbB3, Dr5 and Znf146, using immunohistochemical (IHC) analysis on a tissue microarray that contained 75 BAs and normal gastric and esophageal mucosae samples. BA tissue samples demonstrated overexpression of ErbB3 (42{\%}), Dr5 (90{\%}) and Znf146 (30{\%}) when compared with normal tissues. In conclusion, we have identified and validated several novel proteins that are involved in Barrett's carcinogenesis.",
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