TFF3 trefoil factor 3 (intestinal)

2001-03-01 Catherine Tomasetto Affiliation

I.G.B.M.C., BP 163, 1 rue Laurent Fries, 67404 Illkirch, France

Identity

HGNC

TFF3

LOCATION

21q22.3

LOCUSID

7033

ALIAS

ITF,P1B,TFI

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

3.3 kb gene, 3 exons

Transcription

600 bp

Proteins

Description

precursor 74 amino acids, mature peptide 51 aminoacids, trefoil domain from aminoacids residues 24 to 67. The 74 aminoacids TFF3 protein precusor contains a signal peptide. The mature secreted peptide of 51 aminoacids contains one TFF (TreFoil Factor) domain and one acidic C-terminal domain. The acidic C-terminal domain contains a free cystein residue that promotes homodimerization and heterodimerization.

Expression

Under normal conditions TFF3 is expressed by gobblet cell of the intesine and the colon. TFF3 expression was found in human respiratory tract, human conjunctival goblet cells and in human salivarygland. In addition TFF3 peptive was found in human hypothalamus.

Localisation

In secreterory epithelia TFF3 is expressed by mucin-producing cells. In the brain TFF3 is expressed by a population of neurons of the human hypothamic paraventricular and supraoptic nuclei.

Function

TFF3 promotes migration of epithelial cells in vitro and enhance mucosal healing and epithelial restitutions in vivo in the gastrointestinal mucosa. TFF3 deficient mice aresuceptible to colonic injury induced by standard agents and restitution is impaired. In addition TFF3 deficient mice have an increase in colonocyte apoptosis. The protective action of TFF3 involves activation of both EGF-R and PI3K-Akt pathways. The role of TFF3 in the brain is not clear yet.

Homology

TFF3 belongs to the Trefoil peptide family (TFF) and possesse one TFF1 motif homologous to the TFF motif of TFF1 and TFF2. The TFF motif spans about 40 amino acids and is formed by 6 conserved cysteines residues involved in specific disulfites bridges.

Implicated in

Entity name

Inflamatory bowel diseases, TFF3 is expressed in cancer cells derived from the gastrointestinal tract, in hepatocellular carcinoma cells and in small cell lung carcinoma cells. Like TFF1, TFF3 is expressed in oestrogen-responsive breast cancer cell line and is expressed in breast cancer.

Bibliography

Pubmed ID	Last Year	Title	Authors
8566596	1996	Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.	Babyatsky MW et al
8001677	1995	Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers.	Chinery R et al
9501226	1998	Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.	Efstathiou JA et al
8346203	1993	hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus.	Hauser F et al
10834934	2000	Co-localization of TFF3 peptide and oxytocin in the human hypothalamus.	Jagla W et al
9419349	1998	Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells.	Kanai M et al
7615201	1995	Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.	Kindon H et al
10848594	2000	Distinct pathways of cell migration and antiapoptotic response to epithelial injury: structure-function analysis of human intestinal trefoil factor.	Kinoshita K et al
10476786	1999	Secretory peptides TFF1 and TFF3 synthesized in human conjunctival goblet cells.	Langer G et al
8824194	1996	Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor.	Mashimo H et al
9306961	1997	Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells.	May FE et al
10779222	2000	Mechanisms of regulatory peptide action in the gastrointestinal tract: trefoil peptides.	Podolsky DK et al
9370944	1997	Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.	Poulsom R et al
8815795	1996	The trefoil peptide family.	Sands BE et al
9070946	1997	The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3.	Seib T et al
8463228	1993	Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability.	Semenkovich CF et al
10639160	2000	Intestinal trefoil factor confers colonic epithelial resistance to apoptosis.	Taupin DR et al
9447240	1997	Trefoil peptides: from structure to function.	Thim L et al
10194185	1999	Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.	Wiede A et al

Other Information

Locus ID:

NCBI: 7033
MIM: 600633
HGNC: 11757
Ensembl: ENSG00000160180

Variants:

dbSNP: 7033
ClinVar: 7033
TCGA: ENSG00000160180
COSMIC: TFF3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000160180	ENST00000291525	X6R3S7
ENSG00000160180	ENST00000398431	H7BYT0
ENSG00000160180	ENST00000518498	Q07654

Expression (GTEx)

500

1000

1500

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
25634542	2015	Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study.	72
15665295	2005	Implication of STAT3 signaling in human colonic cancer cells during intestinal trefoil factor 3 (TFF3) -- and vascular endothelial growth factor-mediated cellular invasion and tumor growth.	40
18676680	2008	Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.	32
20237496	2010	New genetic associations detected in a host response study to hepatitis B vaccine.	27
25266665	2014	Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma.	26
19692168	2010	Genetic susceptibility to distinct bladder cancer subphenotypes.	25
21170267	2010	ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression.	25
21170268	2010	Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma.	25
22341453	2012	TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.	25
24045095	2013	Dysregulation of the epigenome in triple-negative breast cancers: basal-like and claudin-low breast cancers express aberrant DNA hypermethylation.	24

Citation

Catherine Tomasetto

TFF3 trefoil factor 3 (intestinal)

Atlas Genet Cytogenet Oncol Haematol. 2001-03-01

Online version: http://atlasgeneticsoncology.org/gene/265/tff3-trefoil-factor-3-(intestinal)