Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice

Sachiyo Nomura, Tammy Baxter, Hirokazu Yamaguchi, Charles Leys, Andrey B. Vartapetian, James G. Fox, Jeffrey R. Lee, Timothy C. Wang, James R. Goldenring

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Background & Aims: The emergence of oxyntic atrophy and metaplastic cell lineages in response to chronic Helicobacter pylori infection predisposes to gastric neoplasia. We have described a trefoil factor family 2 (TFF2; spasmolytic polypeptide) expressing metaplasia (SPEM) associated with gastric neoplasia in both rodent and human fundus. To examine the relationship of SPEM to the neoplastic process in the H. felis-infected C57BL/6 mouse, we have now studied the association of SPEM-related transcripts with preneoplasia. Methods: SPEM-related transcripts were identified by microarray analysis of amplified cRNA from SPEM, and surface mucous cells were isolated by laser capture microdissection from the same gastric sections from male C57BL/6 mice infected with H. felis for 6 months. Expression of SPEM-related transcripts was assessed by in situ hybridization and quantitative RT-PCR, as well as immunohistochemistry for prothymosin α. Results: Eleven SPEM-related transcripts were identified as detectable only in SPEM. The expression of the SPEM-related transcripts was validated by in situ hybridization and quantitative PCR. One transcript, the noncoding RNA Xist, was only identified in SPEM cells from the infected male mice. Ten of the 11 transcripts as well as TFF2 were also expressed in regions of gastritis cystica profunda. Immunocytochemistry for one of the identified proteins, prothymosin α, demonstrated prominent nuclear staining in SPEM and gastritis cystica profunda. Conclusions: The expression of SPEM-related transcripts in regions of gastritis cystica profunda suggests that SPEM represents a precursor lineage for the development of dysplasia in this animal model of gastric carcinogenesis.

Original languageEnglish (US)
Pages (from-to)582-594
Number of pages13
JournalGastroenterology
Volume127
Issue number2
DOIs
StatePublished - Aug 2004

Keywords

  • SP
  • SPEM
  • TFF2
  • spasmolytic polypeptide
  • spasmolytic polypeptide expressing metaplastic lineage
  • trefoil factor family 2

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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