Trefoil factors

Thim, Lars; May, Felicity E. B.

doi:10.1007/s00018-005-5484-6

Cited by 130 publications

(58 citation statements)

References 67 publications

(214 reference statements)

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“…Correspondingly no TFF2 was detected in human conjunctival goblet cells, the cornea, and the nasolacrimal ducts [7,8,56,57]. The absence of TFF2 in the human retina might be (i) evolutionary determined and TFF2 expression only be found in the retina of lower vertebrates [50,58], (ii) due to structural differences in the TFF trefoil domains [1], or (iii) based on the absence of another factor (e.g. pRB) required for its expression.…”

Section: Discussionmentioning

confidence: 99%

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Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Philippeit¹,

Busch²,

Dünker³

2014

Cell Physiol Biochem

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Background: Recent studies demonstrated that epigenetic mechanisms are involved in the regulation of trefoil factor family (TFF) peptide expression in cancer. In human tissues with endogenous TFF1, TFF2 or TFF3 gene expression, the corresponding promoter is unmethylated and in organs without TFF expression, the promoter of the three genes is highly methylated. Methods: Retinoblastoma (Rb) cell lines were treated with the DNA methyltransferase inhibitor 5-Aza-2`deoxycytidine (5-Aza-dC), the histone deacetylase inhibitor 4-Phenylbutyric acid (PBA) or both and analyzed for changes (i) in TFF mRNA expression by Real-time PCR and (ii) in the methylation status of the TFF promoters by genomic bisulfite sequencing. Results: The degree of promoter methylation correlates with endogenous TFF expression in the retinoblastoma cell lines analyzed. Nearly all Rb cell lines exhibiting high endogenous TFF1 expression displayed low methylation of the CpGs in the corresponding promoter region. Low expression of TFF3 in Rb cell lines is linked with high density methylation of the TFF3 promoter. 5-Aza-dC treatment induced TFF1 and TFF3 expression in nearly all cell lines investigated and combined treatment with PBA further increased this effect. The number of methylated CpG dinucleotides of the TFF promoter is clearly reduced upon treatment with 5-Aza-dC and combined treatment with PBA further extended the degree of demethylation. Conclusion: Our data clearly show that the expression of TFF3 in retinoblastoma cell lines is epigenetically regulated, whereas the level of TFF1 and TFF2 seems to be regulated by other or additional mechanisms.

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Section: Discussionmentioning

confidence: 99%

“…The three known TFF peptides, TFF1 (formerly pS2), TFF2 (formerly spasmolytic protein; SP) and TFF3 (formerly intestinal trefoil factor, ITF) are small, 6.5-14 kDa proteins, which are often secreted together with mucines (for review: [1,2,3]).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Philippeit¹,

Busch²,

Dünker³

2014

Cell Physiol Biochem

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“…The trefoil factor (TFF) family consists of three thermostable and protease-resistant proteins, TFF1, TFF2, and TFF3 [8]. These proteins are thought to play a pivotal role in mucosal protection against damage [9].…”

Section: Introductionmentioning

confidence: 99%

Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: A monocentric cohort study in China

Huang

Xie

et al. 2014

BMC Gastroenterol

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BackgroundThe search for better non-invasive biomarkers for gastric cancer remains ongoing. We investigated the predictive power of serum trefoil factor (TFF) levels as biomarkers for gastric cancer in comparison with the pepsinogen (PG) test.MethodsPatients with gastric cancer, chronic atrophic gastritis (CAG) or chronic non-atrophic gastritis (CNAG), and healthy people were recruited. Serum concentrations of TFFs, PG I, and PG II, as well as the presence of antibodies against Helicobacter pylori, were measured by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristics (ROC) were used to compare the predictive powers of the selected factors.ResultsThe serum concentrations of TFF1, TFF2, and TFF3 in the control groups were significantly lower than those in the gastric cancer group with the exception of TFF2 which was elevated in CAG. The area under the ROC curve for TFF3 was greater than that for the PG I/II ratio (0.81 vs 0.78). TFF3 also had a significantly higher predictive power for distinguishing gastric cancer than the PG test (odds ratio: 10.33 vs 2.57). Moreover, combining the serum TFF3 and PG tests for gastric cancer had better predictive power than either alone.ConclusionsSerum TFF3 may be a better predictor of gastric cancer than the PG test, while the combined testing of serum PG and TFF3 could further improve the efficacy of gastric cancer screening.

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“…Intramolecular disulphide bonds within the sequence cause the formation of the characteristic three-loop structure, called the trefoil domain 1, 2, making TFFs stable molecules that are relatively resistant to proteases. Three mammalian trefoil peptides are known: TFF1 (formerly pS2) and TFF3 (intestinal trefoil peptide) contain one while TFF2 (spasmolytic polypeptide) contains two trefoil domains 3.…”

Section: Introductionmentioning

confidence: 99%

Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up

Markicevic¹,

Džodić²,

Buta³

et al. 2014

Int. J. Med. Sci.

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Background. A role of an estrogen-regulated, autocrine motogenic factor was assumed to be a major biological role of trefoil factor 1 (TFF1) in breast cancer. TFF1 is regarded as a predictive factor for positive response to endocrine therapy in breast cancer patients. The aim of our study was to examine TFF1 level distribution in breast carcinomas in order to distinguish estrogen-independent from estrogen-dependent TFF1 expression and to evaluate clinical usefulness of TFF1 status in early breast cancer during the first 3 years of follow-up.Methods. The study included 226 patients with primary operable invasive early breast carcinomas for whom an equal, a 3-year follow-up was conducted. TFF1 levels as well as estrogen receptor (ER) and progesterone receptor (PR) levels were measured in cytosolic extracts of tumor samples by immunoradiometric assay or by use of classical biochemical method, respectively. Non-parametric statistical tests were applied for data analyses.Results. Statistical analysis revealed that TFF1 levels were significantly higher in premenopausal patients (p=0.02), or in tumors with: lower histological grade (p<0.001), positive ER or PR status (p<0.001, in both cases). On the basis of TFF1 level distribution between ER-negative and ER-positive postmenopausal patients with tumors of different histological grade, 14 ng/mg was set as the cut-off value to distinguish estrogen-independent from estrogen-dependent TFF1 expression in breast cancer. Depending on menopausal and PR status, positive TFF1 status identified patients at opposite risk for relapse among ER-positive patients with grade II tumors. Among ER- and PR-positive premenopausal patients with grade II tumors, TFF1 status alone identified patients at opposite risk for relapse.Conclusions. Determination of TFF1 status might identify patients at different risk for relapse and help in making decision on administering adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.

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Trefoil factors

Cited by 130 publications

References 67 publications

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: A monocentric cohort study in China

Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up

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