Disease relevance of TFF1

• In flow cytometry, H. pylori bound to the TFF1 dimer, but Campylobacter jejuni strains and the laboratory strain of E. coli, HB101, did not bind [1].
• Helicobacter pylori interacts with the human single-domain trefoil protein TFF1 [1].
• Expression of TFF1, a cellular motogen, was correlated with estrogen receptor in screen-detected but not interval cancers and was expressed at markedly higher levels in interval breast tumors, the group that expresses lower levels of estrogen receptor [2].
• Accordingly, TFF1 expression is absent in normal human colon crypts but is induced in correlation with Cdc25a and b transcript levels and tumor grade in familial and sporadic colon adenomas and carcinomas [3].
• We propose that TFF1 and Cdc25A-B cooperate with other dominant oncogenic pathways to induce the adenoma and adenocarcinoma transitions [3].

Psychiatry related information on TFF1

• Mutations in genes encoding presenilins (PS1 and PS2) cosegregate with the majority of early onset cases of familial Alzheimer's disease [4].
• From the results of the present study we can conclude that i) a significant interaction between Cath-D and pS2 was found in this case series; ii) the prognostic relationship should not be underestimated in clinical decision making; iii) a predictive score obtained considering the contribution of PgR, pS2 and Cath-D could be useful for clinical use [5].

High impact information on TFF1

• Consistent with a repressive role for PADI4, this enzyme is recruited to the pS2 promoter following hormone induction when the gene is transcriptionally downregulated [6].
• This modification appears on the estrogen-regulated pS2 promoter when the CARM1 methyltransferase is recruited during transcriptional activation [6].
• We provide here a comprehensive picture of events resulting in transcriptional activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells [7].
• Moreover, transcription of the resident estrogen-induced pS2 gene was partially inhibited by exposing MCF-7 cells to progestins or glucocorticoids [8].
• Deletion of the N-terminal domain (region A/B) has no effect on activation of a reporter gene containing a vitellogenin estrogen-responsive element (ERE) and the HSV-tk promoter, whereas it severely impairs activation of the human pS2 gene promoter [9].

Chemical compound and disease context of TFF1

• To examine the transforming potential of TFF1 in human colon epithelial cells, premalignant PC/AA/C1 adenoma cells (PC) derived from a patient with familial adenomatous polyposis (FAP) were transformed by the TFF1 cDNA and used as a model of the adenoma-carcinoma transition [3].
• Primary mucinous carcinomas of the skin express TFF1, TFF3, estrogen receptor, and progesterone receptors [10].
• The human spasmolytic protein, SML1/hSP, an inhibitor of spasmolytic activity and gastric acid secretion in the pig, has been shown to exhibit homology to the pS2 protein, an estrogen-dependent breast cancer marker [11].
• PURPOSE: Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors [12].
• The pS2 protein was not induced by E2 in the 5 ovarian carcinoma cell lines examined [13].

Biological context of TFF1

• We hypothesized that H. pylori interacting with TFF1 could explain the tropism of this bacteria for gastric tissue [1].
• These results show that although both stimuli lead to TFF1 gene activation, estradiol and TPA exert their effects on TFF1 gene expression by different mechanisms [14].
• Interval cancers are characterized by high levels of expression of TFF1 and/or Ki67 suggesting that cell migration and cell division play important roles in the rapid progression of interval cancers [2].
• Constitutive expression of TFF1 increased anchorage-independent cell growth in soft agar, and induced or potentiated the growth of colon PC-TFF1 and kidney MDCKts.src-TFF1 tumor xenografts in athymic mice [3].
• TFF1 and TFF2 proteins were localised by immunochemistry [15].

Anatomical context of TFF1

• CONCLUSIONS: Most of TFF1 in normal human gastric mucosa is present in a complex that is stabilised by a disulphide bond [16].
• Trefoil factor family peptides TFF1, TFF2, and TFF3 exert protective, curative, and tumour suppressive functions in the gastrointestinal tract [17].
• MUC5AC and TFF1 were present as expected in gastric foveolar cells but in addition, MUC2 core antigen, normally present only in the Golgi of intestinal goblet cells, was expressed in secretory granules [18].
• Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines [19].
• CONCLUSIONS: The epithelium of the nasolacrimal ducts synthesizes TFF3 and in some cases also TFF1 [20].

Associations of TFF1 with chemical compounds

• In chromatin immunoprecipitation assays, estradiol treatment resulted in the association of the estrogen receptor-alpha (ERalpha) and acetylated H3 with the TFF1 promoter [14].
• In some instances, proteins were fractionated by caesium chloride density gradient centrifugation prior to detection of TFF1 [16].
• METHODS: TFF1 was detected in normal gastric mucosa and adherent mucus by western transfer analysis after electrophoresis on reducing and non-reducing polyacrylamide gels [16].
• Secretory TFF (trefoil factor family) peptides TFF1, TFF2 and TFF3 are well known for their potent protective and healing effects after mucosal damage (function as 'luminal surveillance peptides') [21].
• TFF2-treated MCF-7 colonies showed a 30% reduction in the number of apoptotic bodies, corroborated by trypan blue exclusion and DNA fragmentation ELISA, indicating TFF2 promotes cell survival via inhibition of apoptosis and can act as a morphogen in the presence of TFF1 [22].

Physical interactions of TFF1

• The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa [23].
• Our results suggest COBRA1 as a novel oncogene in UGCs that regulate AP-1 binding and the expression of TFF1 in upper gastric epithelia [24].
• Furthermore, partial digestion of the A2 and pS2 ERE-bound ER with chymotrypsin or trypsin produced distinct protease cleavage patterns [25].

Enzymatic interactions of TFF1

• The highest pS2 protein level observed in ER-negative unfavorable subgroups (15 ng/mg) was considered as the cut-off value which defined estrogen-regulated expression of pS2 protein [26].
• It was shown that the full-length PS-2 protein is phosphorylated constitutively within its N-terminal domain by casein kinases, whereas the PS-1 protein is not [27].

Regulatory relationships of TFF1

• TFF2 is co-expressed with TFF1 in gastric surface epithelial cells, but its potential role in vivo is unclear [22].
• TFF3 was expressed in the ampulla of Vater. mRNA expression of TFF1 was detected in only approximately 25% of the investigated samples [28].
• Transcription factor GATA-6 activates expression of gastroprotective trefoil genes TFF1 and TFF2 [29].
• Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses [30].
• The interference of toxaphene with the ER mediated responses was supported by a significant suppression of endogenously expressed pS2 RNA and decreased levels of secreted pS2 protein [31].

Other interactions of TFF1

• Relatively large amounts of TFF3-but not TFF1 and TFF2-are present in the posterior lobe of the human pituitary, where it is probably released into the bloodstream [32].
• The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3 [33].
• TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini [34].
• Of 20 ductal adenocarcinomas, TFF1 and EGFR were moderately or strongly expressed in 16 and 12, respectively [35].
• All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells [36].

Analytical, diagnostic and therapeutic context of TFF1

• Recombinant human TFF1 expressed in Escherichia coli was purified by affinity chromatography, ion-exchange chromatography, and gel filtration [1].
• The location of TFF1 in gastric mucosa with an intact adherent mucus layer was assessed by immunohistochemistry [16].
• Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis [15].
• Data yielded by immunohistochemistry and RT-PCR showed a good correlation for both TFF1 and TFF2 [36].
• In isolated human and rat islets, TFF3 and TFF1 mRNA was identified by RT-PCR, and TFF3 protein was detected in human pancreas and islets by ELISA [37].

References