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FLASH GENE
Symbol TFF1 contributors: mct - updated : 09-11-2015
HGNC name trefoil factor 1
HGNC id 11755
Location 21q22.3      Physical location : 43.782.390 - 43.786.644
Synonym name
  • breast cancer, estrogen-inducible sequence expressed in
  • protein pS2
  • gastrointestinal trefoil protein pS2
    • Synonym symbol(s) BCEI, HPS2, PNR2, pS2, HP1.A, pNR-2, D21S21
    DNA
    TYPE functioning gene
    STRUCTURE 4.25 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D21S15 ,D21S101 - D21S231 - D21S53 ,D21S39 ,D21S51 - [D21S64 - MX1 - MX2 - D21S212 ],D21S40 - TFF3 - TFF2 - TFF1 ,D21S56 - [D21S19 ,D21S42 ,D21S113 ], (D21S41 ,D21S43 ) - CBS - CRYAA - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 508 - 84 - 2003 12891554
    EXPRESSION
    Type
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     stomach   predominantly
    Reproductivefemale systembreastmammary gland highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium  
    Epithelialbarrier/lininguroepithelium  
    Epithelialsecretoryglandularexocrine 
    cell lineage
    cell lines breast cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a P-type trefoil domain
  • three intrachain disulfide bonds, forming the three leaf structure
    • isoforms Precursor a 24 aa signal peptide (2.5 kda), a 59 aa mature peptide (6.7 kda)
    HOMOLOGY
    interspecies homolog to rattus Tff1 (65.4pc)
    homolog to murine Tff1 (66.7pc)
    Homologene
    FAMILY
  • trefoil family
    • CATEGORY immunity/defense , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • involved in the mucosal integrity
  • potential candidate to counterbalance the proliferative effects of gastrin
  • potential interest of TFF1 or related peptides to prevent cell death in ocular surface disorders
  • may enhance mucosal healing by modulating motogenic activity, inhibiting apoptosis, and promoting angiogenesis
  • possesses oncogenic functions in mammary carcinoma cells
  • does not exhibit oncogenic properties, but rather reduces tumor development
  • involved in maintaining the gastrointestinal epithelium by serving a tumor-suppressive role
  • acts as a promoter of tumorigenesis in the context of prostate and pancreatic cancers by suppressing oncogene-induced senescence (OIS)
  • soluble factor designed to act mainly to antagonize the OIS process to accelerate tumorigenesis
  • may be considered to be an example of an antisenescence factor that could play a critical role in overcoming the OIS barrier
  • GKN1 is a secreted protein with similar expression and biological functions to TFF1
  • TFF1 inhibited cell proliferation by delaying G1-S phase transition but not by inducing apoptosis
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS digestion , immunity/defense
    text cell growth and maintenance
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
  • heterodimer comprises one molecule each of TFF1 and GKN2, and the disulfide bond between TFF1 and GKN2 is the most important factor stabilizing the heterodimer
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between GKN2 and TFF1 can have synergistic antiproliferative and pro-apoptotic effects on gastric cancer
    • cell & other
    REGULATION
    induced by by gastrin in a gastric cancer cell line
    Other regulated by the gastrin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in primary gastric cancer
    tumoral       loss of function
    in breast (tract, digestive) cancer, and some digestive tumors (stomach, pancreas, biliary tract)
    tumoral     --low  
    in gastric tumors in which tumors exhibited overexpression of CEBPB
    tumoral     --over  
    by hypomethylation of the promoter/enhancer region, significantly lower in prostate carcinoma compared to benign prostatic hyperplasia
    tumoral     --low  
    TFF1 expression is significantly downregulated in gastric cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker overexpression and promoter hypomethylation of trefoil factors may serve as biomarkers in prostate carcinoma
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    Functional antagonism of TFF1 can therefore be considered as a novel therapeutic strategy for mammary carcinoma
    ANIMAL & CELL MODELS