Molecular Alterations in the Stomach of Tff1 -Deficient Mice: Early Steps in Antral Carcinogenesis

TFF1 is a peptide of the gastric mucosa co-secreted with the mucin MUC5AC. It plays a key role in gastric mucosal protection and repair. -deficient ( ) mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas. Thus, these mice represent a model for gastric tumorigenesis. H...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-01, Vol.21 (2), p.644
Main Authors: Znalesniak, Eva B, Salm, Franz, Hoffmann, Werner
Format: Article
Language:English
Subjects:
Adenoma
Animals
Carcinogenesis
Carcinogens
Carcinoma
Cysteine
Fc receptors
fcgbp
Gastric cancer
Gastric mucosa
Gene expression
Immunoglobulin G
inflammation
innate immunity
Mucin
Oxidative stress
Peptides
Polymerase chain reaction
Proteins
Residues
ros
Stomach
tff1
tff2
Transcription
trefoil factor
Tumorigenesis
Tumors
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Summary:TFF1 is a peptide of the gastric mucosa co-secreted with the mucin MUC5AC. It plays a key role in gastric mucosal protection and repair. -deficient ( ) mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas. Thus, these mice represent a model for gastric tumorigenesis. Here, we compared the expression of selected genes in mice and the corresponding wild-type animals (RT-PCR analyses). Furthermore, we systematically investigated the different molecular forms of Tff1 and its heterodimer partner gastrokine-2 (Gkn2) in the stomach (Western blot analyses). As a hallmark, a large portion of murine Tff1 occurs in a monomeric form. This is unexpected because of its odd number of seven cysteine residues. Probably the three conserved acid amino acid residues (EEE) flanking the 7th cysteine residue allow monomeric secretion. As a consequence, the free thiol of monomeric Tff1 could have a protective scavenger function, e.g., for reactive oxygen/nitrogen species. Furthermore, a minor subset of Tff1 forms a disulfide-linked heterodimer with IgG Fc binding protein (Fcgbp). Of special note, in animals a homodimeric form of Gkn2 was observed. In addition, animals showed strongly reduced transcript and protein levels, which might explain their increased sensitivity to infection.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21020644