Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas

Andrew D. Beckler, James K. Roche, Jeffrey C. Harper, Gina Petroni, Henry F. Frierson, Christopher A. Moskaluk, Wael El-Rifai, Steven M. Powell

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

BACKGROUND. Gastric carcinoma is one of the leading causes of cancer-related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas. METHODS. The authors studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry. RESULTS. Strikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified. CONCLUSIONS. These findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas.

Original languageEnglish (US)
Pages (from-to)2184-2191
Number of pages8
JournalCancer
Volume98
Issue number10
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

Fingerprint

Stomach
Carcinoma
Gastric Mucosa
Neoplasms
Genes
Mutation
Proteins
Trefoil Factor-1
Reverse Transcriptase Polymerase Chain Reaction
DNA Sequence Analysis
Real-Time Polymerase Chain Reaction
Mucous Membrane
Immunohistochemistry
RNA
Messenger RNA
DNA
Growth

Keywords

  • DNA sequence
  • Gastric carcinoma
  • Immunohistochemistry
  • Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
  • Trefoil factor 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Beckler, A. D., Roche, J. K., Harper, J. C., Petroni, G., Frierson, H. F., Moskaluk, C. A., ... Powell, S. M. (2003). Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas. Cancer, 98(10), 2184-2191. https://doi.org/10.1002/cncr.11789

Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas. / Beckler, Andrew D.; Roche, James K.; Harper, Jeffrey C.; Petroni, Gina; Frierson, Henry F.; Moskaluk, Christopher A.; El-Rifai, Wael; Powell, Steven M.

In: Cancer, Vol. 98, No. 10, 15.11.2003, p. 2184-2191.

Research output: Contribution to journalArticle

Beckler, AD, Roche, JK, Harper, JC, Petroni, G, Frierson, HF, Moskaluk, CA, El-Rifai, W & Powell, SM 2003, 'Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas', Cancer, vol. 98, no. 10, pp. 2184-2191. https://doi.org/10.1002/cncr.11789
Beckler AD, Roche JK, Harper JC, Petroni G, Frierson HF, Moskaluk CA et al. Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas. Cancer. 2003 Nov 15;98(10):2184-2191. https://doi.org/10.1002/cncr.11789
Beckler, Andrew D. ; Roche, James K. ; Harper, Jeffrey C. ; Petroni, Gina ; Frierson, Henry F. ; Moskaluk, Christopher A. ; El-Rifai, Wael ; Powell, Steven M. / Decreased Abundance of Trefoil Factor 1 Transcript in the Majority of Gastric Carcinomas. In: Cancer. 2003 ; Vol. 98, No. 10. pp. 2184-2191.
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abstract = "BACKGROUND. Gastric carcinoma is one of the leading causes of cancer-related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas. METHODS. The authors studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry. RESULTS. Strikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified. CONCLUSIONS. These findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas.",
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