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Gene Review

TFF3  -  trefoil factor 3 (intestinal)

Homo sapiens

Synonyms: HITF, ITF, Intestinal trefoil factor, P1B, Polypeptide P1.B, ...
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Disease relevance of TFF3


Psychiatry related information on TFF3


High impact information on TFF3


Chemical compound and disease context of TFF3


Biological context of TFF3


Anatomical context of TFF3

  • MUC2 and TFF3 were colocalised throughout the large and small bowel mucosa [17].
  • Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium [2].
  • CONCLUSIONS: This finding in oesophageal carcinoma contrasts with the situation found in normal and neoplastic stomach epithelium where TFF1 and TFF2 are found co-expressed and TFF3 remains silent [18].
  • Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axis [16].
  • This indicates the special requirement, particularly of the esophagogastric junction, for TFF3-triggered protection and repair [16].

Associations of TFF3 with chemical compounds

  • TFF3 expression was analyzed by RT-PCR, Northern blot, and radioimmunoassay (RIA) in relation to cell growth in subclones of HT-29 cells including the CL.16E and methotrexate (MTX) cell lines, which both exhibit a phenotype of mucus-secreting intestinal cells [19].
  • The core of the trefoil domain in hITF consists of a two-stranded antiparallel beta-sheet (Cys 36 to Asp 39 and Trp 47 to Lys 50), which is capped by an irregular loop and forms a central hairpin (loop 3) [20].
  • TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa [21].
  • TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2 [21].
  • TFF1 and TFF3 transcriptional response to X-irradiation differed from that to H2O2 or ES in the timing of their induction as well as tissue-type dependence, i.e., their induction pattern after X-irradiation was late and sustained, whereas their induction by H2O2 or ES was early and transient [22].

Physical interactions of TFF3

  • Although only one consensus STAT6 binding site is contained in the TFF3 gene, located in the intron 1, it did not operate as an enhancer in the context of an SV40 promoter/luciferase construct [23].

Co-localisations of TFF3

  • TFF3 immunoreactivity was colocalized with insulin and glucagon in distinct cell clusters in human fetal pancreas at wk 14 and in the newborn rat pancreas [24].

Regulatory relationships of TFF3


Other interactions of TFF3


Analytical, diagnostic and therapeutic context of TFF3


  1. 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. Rivat, C., Christine, R., Rodrigues, S., Sylvie, R., Bruyneel, E., Erik, B., Piétu, G., Geneviève, P., Robert, A., Amélie, R., Redeuilh, G., Gérard, R., Bracke, M., Marc, B., Gespach, C., Christian, G., Attoub, S., Samir, A. Cancer Res. (2005) [Pubmed]
  2. Localization of TFF3, a new mucus-associated peptide of the human respiratory tract. Wiede, A., Jagla, W., Welte, T., Köhnlein, T., Busk, H., Hoffmann, W. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  3. Primary mucinous carcinomas of the skin express TFF1, TFF3, estrogen receptor, and progesterone receptors. Hanby, A.M., McKee, P., Jeffery, M., Grayson, W., Dublin, E., Poulsom, R., Maguire, B. Am. J. Surg. Pathol. (1998) [Pubmed]
  4. Expression of TFF1, TFF2 and TFF3 in gastric cancer. Kirikoshi, H., Katoh, M. Int. J. Oncol. (2002) [Pubmed]
  5. Trefoil factors and human gastric cancer (review). Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
  6. The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma. Tumuluri, V., Thomas, G.A., Fraser, I.S. J. Oral Pathol. Med. (2004) [Pubmed]
  7. Mitogen-activated protein kinase activation regulates intestinal epithelial differentiation. Taupin, D., Podolsky, D.K. Gastroenterology (1999) [Pubmed]
  8. Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein. Kindon, H., Pothoulakis, C., Thim, L., Lynch-Devaney, K., Podolsky, D.K. Gastroenterology (1995) [Pubmed]
  9. The trefoil peptide family. Sands, B.E., Podolsky, D.K. Annu. Rev. Physiol. (1996) [Pubmed]
  10. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells. Efstathiou, J.A., Noda, M., Rowan, A., Dixon, C., Chinery, R., Jawhari, A., Hattori, T., Wright, N.A., Bodmer, W.F., Pignatelli, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. A second trefoil protein, ITF/hP1.B, is transcribed in human breast cancer. Theisinger, B., Seitz, G., Dooley, S., Welter, C. Breast Cancer Res. Treat. (1996) [Pubmed]
  12. Anti-sense trefoil factor family-3 (intestinal trefoil factor) inhibits cell growth and induces chemosensitivity to adriamycin in human gastric cancer cells. Chan, M.W., Chan, V.Y., Leung, W.K., Chan, K.K., To, K.F., Sung, J.J., Chan, F.K. Life Sci. (2005) [Pubmed]
  13. The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family. Chinery, R., Williamson, J., Poulsom, R. Genomics (1996) [Pubmed]
  14. Mouse Trefoil factor genes: genomic organization, sequences and methylation analyses. Ribieras, S., Lefèbvre, O., Tomasetto, C., Rio, M.C. Gene (2001) [Pubmed]
  15. Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression. Gött, P., Beck, S., Machado, J.C., Carneiro, F., Schmitt, H., Blin, N. Eur. J. Hum. Genet. (1996) [Pubmed]
  16. Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axis. Kouznetsova, I., Kalinski, T., Peitz, U., Mönkemüller, K.E., Kalbacher, H., Vieth, M., Meyer, F., Roessner, A., Malfertheiner, P., Lippert, H., Hoffmann, W. Cell Tissue Res. (2007) [Pubmed]
  17. Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa. Longman, R.J., Douthwaite, J., Sylvester, P.A., Poulsom, R., Corfield, A.P., Thomas, M.G., Wright, N.A. Gut (2000) [Pubmed]
  18. Differential expression of mucins and trefoil peptides in native epithelium, Barrett's metaplasia and squamous cell carcinoma of the oesophagus. Labouvie, C., Machado, J.C., Carneiro, F., Sarbia, M., Vieth, M., Porschen, R., Seitz, G., Blin, N. J. Cancer Res. Clin. Oncol. (1999) [Pubmed]
  19. Expression of human TFF3 in relation to growth of HT-29 cell subpopulations: involvement of PI3-K but not STAT6. Durual, S., Blanchard, C., Estienne, M., Jacquier, M.F., Cuber, J.C., Perrot, V., Laboisse, C., Cuber, J.C. Differentiation (2005) [Pubmed]
  20. High-resolution solution structure of human intestinal trefoil factor and functional insights from detailed structural comparisons with the other members of the trefoil family of mammalian cell motility factors. Lemercinier, X., Muskett, F.W., Cheeseman, B., McIntosh, P.B., Thim, L., Carr, M.D. Biochemistry (2001) [Pubmed]
  21. A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa. Kouznetsova, I., Peitz, U., Vieth, M., Meyer, F., Vestergaard, E.M., Malfertheiner, P., Roessner, A., Lippert, H., Hoffmann, W. Cell Tissue Res. (2004) [Pubmed]
  22. Coordinate late expression of trefoil peptide genes (pS2/TFF1 and ITF/TFF3) in human breast, colon, and gastric tumor cells exposed to X-rays. Balcer-Kubiczek, E.K., Harrison, G.H., Xu, J.F., Gutierrez, P.L. Mol. Cancer Ther. (2002) [Pubmed]
  23. IL-4 and IL-13 up-regulate intestinal trefoil factor expression: requirement for STAT6 and de novo protein synthesis. Blanchard, C., Durual, S., Estienne, M., Bouzakri, K., Heim, M.H., Blin, N., Cuber, J.C. J. Immunol. (2004) [Pubmed]
  24. Trefoil factors are expressed in human and rat endocrine pancreas: differential regulation by growth hormone. Jackerott, M., Lee, Y.C., M??llg??rd, K., Kofod, H., Jensen, J., Rohleder, S., Neubauer, N., Gaarn, L.W., Lykke, J., Dodge, R., Dalgaard, L.T., S??strup, B., Jensen, D.B., Thim, L., Nex??, E., Thams, P., Bisgaard, H.C., Nielsen, J.H. Endocrinology (2006) [Pubmed]
  25. Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. Liu, D., el-Hariry, I., Karayiannakis, A.J., Wilding, J., Chinery, R., Kmiot, W., McCrea, P.D., Gullick, W.J., Pignatelli, M. Lab. Invest. (1997) [Pubmed]
  26. Trefoil factor family (TFF) peptides of normal human Vater's ampulla. Paulsen, F., Varoga, D., Paulsen, A., Tsokos, M. Cell Tissue Res. (2005) [Pubmed]
  27. Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas. Hamada, A., Mankovskaya, S., Saenko, V., Rogounovitch, T., Mine, M., Namba, H., Nakashima, M., Demidchik, Y., Demidchik, E., Yamashita, S. Cancer Lett. (2005) [Pubmed]
  28. Trefoil peptide expression and secretion is regulated by neuropeptides and acetylcholine. Ogata, H., Podolsky, D.K. Am. J. Physiol. (1997) [Pubmed]
  29. Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma. Khoury, T., Chadha, K., Javle, M., Donohue, K., Levea, C., Iyer, R., Okada, H., Nagase, H., Tan, D. International journal of gastrointestinal cancer. (2005) [Pubmed]
  30. Trefoil peptides promote restitution of wounded corneal epithelial cells. Göke, M.N., Cook, J.R., Kunert, K.S., Fini, M.E., Gipson, I.K., Podolsky, D.K. Exp. Cell Res. (2001) [Pubmed]
  31. Expression of mRNA of trefoil factor peptides in human nasal mucosa. Lee, S.H., Lee, S.H., Oh, B.H., Lee, H.M., Choi, J.O., Jung, K.Y. Acta Otolaryngol. (2001) [Pubmed]
  32. Specific secretion of gel-forming mucins and TFF peptides in HT-29 cells of mucin-secreting phenotype. Gouyer, V., Wiede, A., Buisine, M.P., Dekeyser, S., Moreau, O., Lesuffleur, T., Hoffmann, W., Huet, G. Biochim. Biophys. Acta (2001) [Pubmed]
  33. 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., Poulsom, R., Chinery, R., Rogers, L.A., Hanby, A.M., Wright, N.A., Hoffmann, W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  34. Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Dhar, D.K., Wang, T.C., Tabara, H., Tonomoto, Y., Maruyama, R., Tachibana, M., Kubota, H., Nagasue, N. Clin. Cancer Res. (2005) [Pubmed]
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