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


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 alpha, 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.
Nomura
Sachiyo
S
Nashville VA Medical Center and the Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Tennessee, USA.
Baxter
Tammy
T
Yamaguchi
Hirokazu
H
Leys
Charles
C
Vartapetian
Andrey B
AB
Fox
James G
JG
Lee
Jeffrey R
JR
Wang
Timothy C
TC
Goldenring
James R
JR
D000818:Animals; D016481:Helicobacter Infections / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D044922:Helicobacter felis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
D036341:Intercellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; C040782:prothymosin alpha; C451060:spasmolytic polypeptide; D013947:Thymosin