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Catherine Tomasetto - One of the best experts on this subject based on the ideXlab platform.
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inhibition of cyclooxygenase 2 causes regression of gastric adenomas in Trefoil Factor 1 deficient mice
International Journal of Cancer, 2012Co-Authors: Catherine Tomasetto, Alexandra Thiel, Kirsi Narko, Mira Heinonen, Annabrita Hemmes, Mariechristine RioAbstract:Cyclooxygenase-2 (Cox-2) expression is a marker of reduced survival in gastric cancer patients, and inhibition of Cox-2 suppresses gastrointestinal carcinogenesis in experimental animal models. To investigate the role of Cox-2 in gastric carcinogenesis in vivo, we utilized Trefoil Factor 1 (Tff1) deficient mice, which model the neoplastic process of the stomach by developing gastric adenomas with full penetrance. These tumors express Cox-2 protein and mRNA, and we have now investigated the effects of genetic deletion of the mouse Cox-2 gene [also known as prostaglandin-endoperoxide synthase 2 (Ptgs2)] and a Cox-2 selective drug celecoxib. Our results show that genetic deletion of Cox-2 in the Tff1 deleted background resulted in reduced adenoma size and ulceration with a chronic inflammatory reaction at the site of the adenoma. To characterize the effect of Cox-2 inhibition in more detail, mice that had already developed an adenoma were fed with celecoxib for 8-14 weeks, which resulted in disruption of the adenoma that ranged from superficial erosion to deep ulcerated destruction accompanied with chronic inflammation. Importantly, mice fed with celecoxib for 16 weeks, followed by control food for 9 weeks, redeveloped a complete adenoma with no detectable inflammatory process. Finally, we determined the identity of the Cox-2 expressing cells and found them to be fibroblasts. Our results show that inhibition of Cox-2 is sufficient to reversibly disrupt gastric adenomas in mice.
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deficiency in Trefoil Factor 1 tff1 increases tumorigenicity of human breast cancer cells and mammary tumor development in tff1 knockout mice
Oncogene, 2011Co-Authors: Emilie Buache, Mariepierre Chenard, Nicolas Etique, Fabien Alpy, Isabelle Stoll, M Muckensturm, B Reinasanmartin, Catherine TomasettoAbstract:Although Trefoil Factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors.
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inhibition of gastric carcinogenesis by the hormone gastrin is mediated by suppression of tff1 epigenetic silencing
Gastroenterology, 2011Co-Authors: Hiroyuki Tomita, Guangchun Jin, Shigeo Takaishi, Trevelyan R Menheniott, Xiangdong Yang, Wataru Shibata, Kelly S Betz, Kazuyuki Kawakami, Toshinari Minamoto, Catherine TomasettoAbstract:Background & Aims Epigenetic alterations have been correlated with field cancerization in human patients, but evidence from experimental models that specific epigenetic changes can initiate cancer has been lacking. Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone gastrin exerts a suppressive effect on antral gastric carcinogenesis. Methods N -methyl- N -nitrosourea (MNU)-dependent gastric cancer was investigated in hypergastrinemic (INS-GAS), gastrin-deficient (GAS −/− ), Tff1-deficient (Tff1 +/− ), and wild-type (WT) mice. Epigenetic alterations of the Trefoil Factor 1 (TFF1) tumor suppressor gene were evaluated in vitro and in vivo. Results Human intestinal-type gastric cancers in the antrum exhibited progressive TFF1 repression and promoter hypermethylation. Mice treated with MNU exhibited a field defect characterized by widespread Tff1 repression associated with histone H3 lysine 9 methylation and H3 deacetylation at the Tff1 promoter in epithelial cells. In MNU-induced advanced cancers, DNA methylation at the Tff1 promoter was observed. Tumor induction and Tff1 repression were increased in MNU-treated mice by Helicobacter infection. Hypergastrinemia suppressed MNU-dependent tumor initiation and progression in a manner that correlated with gene silencing and epigenetic alterations of Tff1 . In contrast, homozygous gastrin-deficient and heterozygous Tff1 -deficient mice showed enhanced MNU-dependent field defects and cancer initiation compared with WT mice. In gastric cancer cells, gastrin stimulation partially reversed the epigenetic silencing in the TFF1 promoter. Conclusions Initiation of antral gastric cancer is associated with progressive epigenetic silencing of TFF1 , which can be suppressed by the hormone gastrin.
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TFF1 (Trefoil Factor 1)
Atlas of genetics and cytogenetics in oncology and haematology, 2011Co-Authors: Catherine TomasettoAbstract:Review on TFF1 (Trefoil Factor 1), with data on DNA, on the protein encoded, and where the gene is implicated.
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Amplification and invasiveness of epithelial progenitors during gastric carcinogenesis in Trefoil Factor 1 knockout mice.
Cell Proliferation, 2008Co-Authors: Sherif Karam, Catherine Tomasetto, Mariechristine RioAbstract:OBJECTIVE: It is not known whether or not epithelial progenitors of the pyloric antrum are involved in gastric carcinogenesis. Normally, these progenitors give rise to two main cell lineages: pit and gland mucous cells. This study was designed to examine the changes that occur in pyloric antral mucous cell lineages and their progenitors during development of gastric adenoma and carcinoma in Trefoil Factor 1 (TFF1) knockout mice. MATERIALS AND METHODS: Pyloric antral mucosal tissues of TFF1 knockout mice at ages from 3 days to 17 months were processed for histochemical analysis using Ulex europaeus and Grifforia simplifolica lectins as markers for pit and gland mucous cells, respectively. The dividing epithelial progenitors were identified by using immunohistochemical and electron microscopy techniques. RESULTS: TFF1 loss was associated with amplification of both mucus-secreting pit and gland cells. Both lectins examined bound not only to mature mucous cells, but also to most of epithelial progenitors which gradually amplified with age and frequently were seen in mitosis. Analysis of 12- to 17-month-old TFF1-deficient stomachs revealed occasional groups of poorly differentiated mucosal cells with features similar to those of epithelial progenitors (or stem cells), in the basal portion of the antral mucosa. These cells eventually invaded the muscularis mucosa while maintaining some capacity to differentiate. CONCLUSION: This study shows that the progenitors of pit and gland mucous cells contribute to gastric carcinogenesis in the pyloric antrum of TFF1 knockout mice, strongly supporting the concept of stem cell origin of cancer.
James R. Davie - One of the best experts on this subject based on the ideXlab platform.
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mitogen and stress activated protein kinases 1 and 2 are required for maximal Trefoil Factor 1 induction
PLOS ONE, 2013Co-Authors: Protiti Khan, Shihua He, Bojan Drobic, Beatriz Perezcadahia, Shannon Healy, James R. DavieAbstract:Mitogen- and stress-activated protein kinases 1 and 2 (MSK1 and MSK2), activated downstream of the ERK- and p38-mitogen-activated protein kinase pathways are involved in cell survival, proliferation and differentiation. Following mitogenic or stress stimuli, they mediate the nucleosomal response, which includes phosphorylation of histone H3 at serine 10 (H3S10ph) coupled with transcriptional activation of immediate-early genes. While MSK1 and MSK2 are closely related, their relative roles may vary with cellular context and/or stimuli. However, our knowledge of MSK2 recruitment to immediate-early genes is limited, as research has primarily focused on MSK1. Here, we demonstrate that both MSK1 and MSK2, regulate the phorbol ester 12-O-tetradecanoylphorbol-13-acetate induced expression of the breast cancer marker gene, Trefoil Factor 1 (TFF1), by phosphorylating H3S10 at its 5′ regulatory regions. The MSK-mediated phosphorylation of H3S10 promotes the recruitment of 14-3-3 isoforms and BRG1, the ATPase subunit of the BAF/PBAF remodeling complex, to the enhancer and upstream promoter elements of TFF1. The recruited chromatin remodeling activity leads to the RNA polymerase II carboxy-terminal domain phosphorylation at the TFF1 promoter, initiating TFF1 expression in MCF-7 breast cancer cells. Moreover, we show that MSK1 or MSK2 is recruited to TFF1 regulatory regions, but as components of different multiprotein complexes.
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association of sp3 and estrogen receptor α with the transcriptionally active Trefoil Factor 1 promoter in mcf 7 breast cancer cells
Journal of Cellular Biochemistry, 2008Co-Authors: James R. DavieAbstract:To further explore the role of Sp1 and Sp3 in the estrogen regulated TFF1 gene transcription, chromatin immunoprecipitation (ChIP) assay was used to determine the association of estrogen receptor alpha (ERalpha), Sp1 and Sp3 with the endogenous Trefoil Factor 1 (TFF1) gene promoter in MCF-7 breast cancer cells. ERalpha and serine 5 phosphorylated RNA polymerase II, the form of RNA polymerase II associated with transcription initiation, were recruited to the TFF1 gene promoter following estrogen addition to MCF-7 cells cultured under estrogen deplete conditions. Both Sp1 and Sp3 were bound to the TFF1 gene promoter before and after estrogen treatment. Using the re-ChIP assay, we demonstrate that either Sp1 or Sp3 but not both bind to a TFF1 promoter. The co-occupancy of ERalpha and Sp1 on TFF1 promoter remains at similar level with and without estrogen, while that of ERalpha and Sp3 increased in the presence of estrogen. Further, we observed increased co-occupancy of Sp3 and serine 5 phosphorylated RNA polymerase II on the TFF1 promoter after estrogen treatment of cells. Taken together, these results provide evidence that Sp3 and ERalpha are involved in the estrogen induced transcription of the TFF1 gene.
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chromatin modification of the Trefoil Factor 1 gene in human breast cancer cells by the ras mitogen activated protein kinase pathway
Cancer Research, 2006Co-Authors: Paula S Espino, Jenny Yu, Lin Li, Shihua He, James R. DavieAbstract:Histone H3 phosphorylation is a downstream response to activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. This modification is thought to have a role in chromatin remodeling and in the initiation of gene transcription. In MCF-7 breast cancer cells, we observed that phosphorylated histone H3 (phospho-H3) at Ser 10 but not Ser 28 increased with phorbol ester (12- O -tetradecanoylphorbol-13-acetate, TPA) treatment. Although phosphorylated extracellular signal-regulated kinase 1/2 levels in these cells cultured under estradiol deplete and replete conditions displayed no change, a significant induction was observed after TPA treatment. Furthermore, whereas both estradiol and TPA increased Trefoil Factor 1 (TFF1) mRNA levels in these cells, only TPA-induced and not estradiol-induced TFF1 expression was inhibited by the H3 kinase mitogen and stress activated protein kinase (MSK) inhibitor H89 and MAPK kinase inhibitor UO126, showing the involvement of the Ras/MAPK following TPA induction. Mutation of the activator protein 1 (AP-1) binding site abrogated the TPA-induced transcriptional response of the luciferase reporter gene under the control of the TFF1 promoter, showing the requirement for the AP-1 site. In chromatin immunoprecipitation assays, estradiol treatment resulted in the association of the estrogen receptor-α (ERα) and acetylated H3 with the TFF1 promoter. The levels of phospho-H3 and MSK1 associated with the TFF1 promoter were moderately increased. In the presence of TPA, whereas ERα was not bound to the promoter, a strong association of acetylated and/or phospho-H3, MSK1, and c-Jun was observed. 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. (Cancer Res 2006; 66(9): 4610-6)
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chromatin modification of the Trefoil Factor 1 gene in human breast cancer cells by the ras mitogen activated protein kinase pathway
Cancer Research, 2006Co-Authors: Paula S Espino, James R. DavieAbstract:Histone H3 phosphorylation is a downstream response to activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. This modification is thought to have a role in chromatin remodeling and in the initiation of gene transcription. In MCF-7 breast cancer cells, we observed that phosphorylated histone H3 (phospho-H3) at Ser(10) but not Ser(28) increased with phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) treatment. Although phosphorylated extracellular signal-regulated kinase 1/2 levels in these cells cultured under estradiol deplete and replete conditions displayed no change, a significant induction was observed after TPA treatment. Furthermore, whereas both estradiol and TPA increased Trefoil Factor 1 (TFF1) mRNA levels in these cells, only TPA-induced and not estradiol-induced TFF1 expression was inhibited by the H3 kinase mitogen and stress activated protein kinase (MSK) inhibitor H89 and MAPK kinase inhibitor UO126, showing the involvement of the Ras/MAPK following TPA induction. Mutation of the activator protein 1 (AP-1) binding site abrogated the TPA-induced transcriptional response of the luciferase reporter gene under the control of the TFF1 promoter, showing the requirement for the AP-1 site. In chromatin immunoprecipitation assays, estradiol treatment resulted in the association of the estrogen receptor-alpha (ERalpha) and acetylated H3 with the TFF1 promoter. The levels of phospho-H3 and MSK1 associated with the TFF1 promoter were moderately increased. In the presence of TPA, whereas ERalpha was not bound to the promoter, a strong association of acetylated and/or phospho-H3, MSK1, and c-Jun was observed. 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.
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estrogen regulation of Trefoil Factor 1 expression by estrogen receptor α and sp proteins
Experimental Cell Research, 2005Co-Authors: Virginia A Spencer, Hou-yu Chen, Jenny Yu, James R. DavieAbstract:Abstract Estrogen-responsive genes in human breast cancer cells often have an estrogen response element (ERE) positioned next to an Sp1 binding site. In chromatin immunoprecipitation (ChIP) assays, we investigated the binding of estrogen receptor α (ER), Sp1, and Sp3 to the episomal and native estrogen-responsive Trefoil Factor 1 (TFF1; formerly pS2) promoter in MCF-7 breast cancer cells. Mutation of the Sp site upstream of the ERE reduced estrogen responsiveness and prevented binding of Sp1 and Sp3, but not ER to the episomal promoter. In the absence of estradiol (E2), Sp1, Sp3, histone deacetylase 1 (HDAC), and HDAC2, and low levels of acetylated H3 and H4 are associated with the native promoter, with the histones being engaged in dynamic reversible acetylation. Following E2 addition, levels of ER and acetylated H3 and H4 bound to the native promoter increases. There is clearance of Sp1, but not of Sp3, from the promoter while HDAC1 and HDAC2 remain bound. These data are consistent with a model in which Sp1 or Sp3 aid in recruitment of HDACs and histone acetyltransferases (HATs) to mediate dynamic acetylation of histones associated with the TFF1 promoter, which is in a state of readiness to respond to events occurring following the addition of estrogen.
Bayasi Guleng - One of the best experts on this subject based on the ideXlab platform.
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mirna423 5p regulates cell proliferation and invasion by targeting Trefoil Factor 1 in gastric cancer cells
Cancer Letters, 2014Co-Authors: Xu Wang, Xiaoning Yang, Bayasi GulengAbstract:National Natural Science Foundation of China [81101817, 81370591, 30971362]; Foundations of Health Bureau of Fujian and Xiamen in China [3502Z200940010]
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mirna423 5p regulates cell proliferation and invasion by targeting Trefoil Factor 1 in gastric cancer cells
Cancer Letters, 2014Co-Authors: Jingjing Liu, Jianlin Ren, Xu Wang, Xiaoning Yang, Yunpeng Liu, Ying Shi, Bayasi GulengAbstract:TFF1 is a small, secreted protein in the TFF family that has a pivotal role as a motogenic Factor in epithelial restitution and cell motility, and as a tumor suppressor gene in the stomach. In this study, we identified TFF1 as a novel target gene of miRNA-423-5p. miRNA-423-5p negatively regulated the expression of TFF1 by binding to its 3'UTR and participated in proliferation/invasion-related processes via a TFF1-dependent manner in gastric cancer cells. Our findings suggested that miR-423-5p may be a novel target for the future development of specific therapeutic interventions for gastric cancer.
Mariechristine Rio - One of the best experts on this subject based on the ideXlab platform.
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inhibition of cyclooxygenase 2 causes regression of gastric adenomas in Trefoil Factor 1 deficient mice
International Journal of Cancer, 2012Co-Authors: Catherine Tomasetto, Alexandra Thiel, Kirsi Narko, Mira Heinonen, Annabrita Hemmes, Mariechristine RioAbstract:Cyclooxygenase-2 (Cox-2) expression is a marker of reduced survival in gastric cancer patients, and inhibition of Cox-2 suppresses gastrointestinal carcinogenesis in experimental animal models. To investigate the role of Cox-2 in gastric carcinogenesis in vivo, we utilized Trefoil Factor 1 (Tff1) deficient mice, which model the neoplastic process of the stomach by developing gastric adenomas with full penetrance. These tumors express Cox-2 protein and mRNA, and we have now investigated the effects of genetic deletion of the mouse Cox-2 gene [also known as prostaglandin-endoperoxide synthase 2 (Ptgs2)] and a Cox-2 selective drug celecoxib. Our results show that genetic deletion of Cox-2 in the Tff1 deleted background resulted in reduced adenoma size and ulceration with a chronic inflammatory reaction at the site of the adenoma. To characterize the effect of Cox-2 inhibition in more detail, mice that had already developed an adenoma were fed with celecoxib for 8-14 weeks, which resulted in disruption of the adenoma that ranged from superficial erosion to deep ulcerated destruction accompanied with chronic inflammation. Importantly, mice fed with celecoxib for 16 weeks, followed by control food for 9 weeks, redeveloped a complete adenoma with no detectable inflammatory process. Finally, we determined the identity of the Cox-2 expressing cells and found them to be fibroblasts. Our results show that inhibition of Cox-2 is sufficient to reversibly disrupt gastric adenomas in mice.
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Amplification and invasiveness of epithelial progenitors during gastric carcinogenesis in Trefoil Factor 1 knockout mice.
Cell Proliferation, 2008Co-Authors: Sherif Karam, Catherine Tomasetto, Mariechristine RioAbstract:OBJECTIVE: It is not known whether or not epithelial progenitors of the pyloric antrum are involved in gastric carcinogenesis. Normally, these progenitors give rise to two main cell lineages: pit and gland mucous cells. This study was designed to examine the changes that occur in pyloric antral mucous cell lineages and their progenitors during development of gastric adenoma and carcinoma in Trefoil Factor 1 (TFF1) knockout mice. MATERIALS AND METHODS: Pyloric antral mucosal tissues of TFF1 knockout mice at ages from 3 days to 17 months were processed for histochemical analysis using Ulex europaeus and Grifforia simplifolica lectins as markers for pit and gland mucous cells, respectively. The dividing epithelial progenitors were identified by using immunohistochemical and electron microscopy techniques. RESULTS: TFF1 loss was associated with amplification of both mucus-secreting pit and gland cells. Both lectins examined bound not only to mature mucous cells, but also to most of epithelial progenitors which gradually amplified with age and frequently were seen in mitosis. Analysis of 12- to 17-month-old TFF1-deficient stomachs revealed occasional groups of poorly differentiated mucosal cells with features similar to those of epithelial progenitors (or stem cells), in the basal portion of the antral mucosa. These cells eventually invaded the muscularis mucosa while maintaining some capacity to differentiate. CONCLUSION: This study shows that the progenitors of pit and gland mucous cells contribute to gastric carcinogenesis in the pyloric antrum of TFF1 knockout mice, strongly supporting the concept of stem cell origin of cancer.
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Copper-binding activity of Trefoil Factor 1 (TFF1): a new perspective in the study of the multifunctional roles of TFFs.
Peptides Peptides (Fayetteville), 2007Co-Authors: Alessandra Tosco, Maria Chiara Monti, Mariechristine Rio, Bianca Fontanella, Luigi Gomez-paloma, Arturo Leone, Liberato MarzulloAbstract:Trefoil Factors (TFFs) are gastrointestinal peptides playing an essential role in the epithelial restitution. Among the three known TFF peptides, TFF1 is characterized by three disulfide bonds producing a compact globular structure and an extended and disordered tail formed by amino- and carboxy-termini. The presence of a cysteine surrounded by several negatively charged residues in this region of the protein, highly conserved in different species, suggests the possible formation of a metal-binding site. Affinity chromatography and mass spectrometric analyses allowed us to demonstrate a selective binding affinity of TFF1 for copper. The binding induces conformational changes in the tertiary structure as demonstrated by circular dichroism experiments, while limited proteolysis revealed an altered access to the cleavage sites in the amino- and carboxy-termini. The results of this study reveal a new property of TFF1 and suggest that copper could influence its biological activities by interfering with the dimerization of the peptide and/or the interaction with mucins or putative TFF receptors.
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Trefoil Factor 1 ps2 tff1 a peptide with numerous functions
Bulletin Du Cancer, 2005Co-Authors: Carole Mathelin, Catherine Tomasetto, Mariechristine RioAbstract:Les peptides en trefle (Trefoil Factors ou TFF) sont au nombre de trois : TFF1 encore appele pS2, TFF2 ou spasmolytic peptide (SP) et TFF3 ou intestinal Trefoil Factor (ITF). Ce sont des peptides exprimes et secretes par les cellules a mucus des epithelia agissant en conditions physiologiques comme des gardiens de l’integrite des muqueuses, en particulier digestives. Lors des agressions bacteriennes, virales ou medicamenteuses ainsi que dans certaines pathologies inflammatoires ou ulcereuses, ils jouent un role cle dans la restitution et la regeneration des muqueuses. A cote de ces fonctions qu’il partage avec les deux autres TFF, pS2/TFF1 presente des fonctions particulieres ; il joue notamment un role de suppresseur de tumeurs gastriques. Enfin, sa surexpression dans differents cancers a ete largement rapportee (sein, colon, prostate, pancreas, thyroide, poumon…). Dans le cas des cancers mammaires, elle constitue un facteur de bon pronostic. De plus, pS2/TFF1 est un marqueur predictif de la reponse aux hormonotherapies anti-estrogeniques.
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Trefoil Factor 1 tff1 ps2 deficiency activates the unfolded protein response
Molecular Medicine, 2002Co-Authors: Luisfernando Torres, Catherine Tomasetto, Sherif M Karam, Corinne Wendling, Mariepierre Chenard, David Kershenobich, Mariechristine RioAbstract:The Trefoil Factor 1 (TFF1/pS2) is a secreted gastrointestinal peptide that is often altered or lost in human gastric cancers. Consistently, mouse TFF1 deficiency leads to antropyloric tumors. To investigate the gene expression alterations in response to the lack of TFF1, we performed differential expression analyses of TFF1 null antropyloric tumors using an array containing 588 cDNAs. Using total and enriched probes, 22 genes were found to be up-regulated. The identification of the genes for endoplasmic reticulum (ER)-resident GRP78, ERp72, and p58IPK proteins connected TFF1 deficiency to the unfolded protein response (UPR). Accordingly, CHOP10, a transcription Factor induced early in response to ER stress, and the pleiotropic Clusterin, involved in protein folding, were also overexpressed. Northern blot analyses of 8 weeks and 1 year TFF1 null tumors confirmed that GRP78, ERp72, p58IPK, CHOP10, and Clusterin overexpression is a common and permanent feature shared by all TFF1 null antropyloric tumors. Finally, consistent with UPR, ultrastructural analyses showed that tumor rough ER was enlarged and contained dense material, supporting the hypothesis that TFF1 deficiency leads to the accumulation of misfolded proteins in the ER. Together, our data provide the first evidence of a relationship between a member of the TFF family and the ER machinery. Whereas to date TFF1 is believed to act as an extracellular molecule, our results suggest a possible additional function for TFF1 in protein folding and/or secretion.
Lin Wang - One of the best experts on this subject based on the ideXlab platform.
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influence of human Trefoil Factor 1 htff1 fusion protein on gastric mucosal lesion in mice after burn injury
Chinese journal of burns, 2008Co-Authors: Lin Wang, Yong Sun, Yong Zhang, Xi PengAbstract:Objective To observe the effect of hTFF1 fusion protein on gastric mucosal lesion in mice after burn injury. Methods The pET32alpha-hTFF1 vector were transfected into E.coli Origami B (DE3), and rhTFF1 fusion protein was expressed by IPTG induction. Mice were inflicted with 30% TBSA full-thickness burn, then were divided into burn treatment (BT, with treatment of rhTEF1 fusion protein by gavage), burn control (BC, with treatment of isotonic saline by gavage), and normal control (NC) groups according to block randomized design. Gastric mucosal lesion, including appearance of gastric mucosa, injury index, pathological change, were compared between BT and BC groups before and after burn injury, and above indices in NC group were also examined. Results The rhTFF1 fusion protein was expressed with good specificity confirmed with Western blot analysis. The gastric erosion rate was 77.8% and 22.2% respectively in BC and T group. The injury index was 6.2 +/- 2.0 and 2.0 +/- 1.2 respectively in BC and T group. Above indices in C group were 0. Conclusion The rhTFF1 fusion protein can be expressed in E.coli expression systems, which can obviously ameliorate gastric mucosal lesion in mice after burn injury.
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molecular forms of Trefoil Factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues
World Journal of Gastroenterology, 2006Co-Authors: Jianlin Ren, Lin Wang, Jinyan Luo, Huaxiu ShiAbstract:AIM: To study the molecular forms of Trefoil Factor 1 (TFF1) in normal gastric mucosa and its expression in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) and the role of TFF1 in the carcinogenesis and progression of gastric carcinoma and its molecular biological mechanism underlying gastric mucosa protection. METHODS: The molecular forms of TFF1 in normal gastric mucosa were observed by Western blot. The expression of TFF1 in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) was also assayed by immunohistochemical method. The average positive AO was estimated by Motic Images Advanced 3.0 software. RESULTS: Three patterns of TFF1 were found in normal gastric mucosa: monomer, dimmer, and TFF1 compound whose molecular weight is about 21 kDa. The concentration of TFF1 compound was the highest among these three patterns. TFF1 was expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum, especially around the nuclei. The closer the TFF1 to the lumen, the higher the expression of TFF1. The expression of TFF1 in peripheral tissue of gastric carcinoma (0.51 ± 0.07) was higher than that in normal gastric mucosa (0.44 ± 0.06, P 0.05). The expression of TFF1 in gastric mucosa with atypical hyperplasia (0.57 ± 0.03) was significantly higher than that in normal gastric mucosa (P 0.05). CONCLUSION: TFF1 is expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum. Its main pattern is TFF1 compound, which may have a greater biological activity than monomer and dimer. The expression of TFF1 in peripheral mucosa of gastric ulcer is higher than that in mucosa 5 cm beyond the ulcer, indicating that TFF1 plays an important part in protection and restitution of gastric mucosa. The expression of TFF1 is increased in peripheral tissues of gastric carcinoma and gastric mucosa with atypical hyperplasia, but is decreased in cancer tissues, implying that TFF1 may be related to suppression and differentiation of carcinoma. The weaker expression of TFF1 in poorly-differentiated carcinoma may be related to the destruction of glands and cells in cancer tissues and the decrease in secretion of TFF1.
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association of Trefoil Factor 1 expression with gastric mucosa injuries and gastric cancer
Academic journal of the first medical college of PLA, 2005Co-Authors: Jianlin Ren, Lin Wang, Jinyan Luo, Jianmin Chen, Huaxiu Shi, Jinshui PanAbstract:Objective To investigate the role of Trefoil Factor 1 (TFF1) expression in gastric mucosa healing and carcinoma suppression. Methods TEF1 expressions in normal and pathological gastric mucosa tissues were detected by immunohistochemical analysis, and the average optical density (OD) was estimated by Motic Images Advanced 3.0 software. Results Increased TFF1 expression was detected in gastritis, gastric ulcer and duodenal ulcer tissues as compared with that in normal gastric mucosa. TFF1 expression was increased in multiple and compound ulcer in comparison with simple ulcer, but there was no significant difference between gastric ulcer and duodenal ulcer, or between gastritis and simple ulcer tissues. Increased TFF1 was also detected in the mucosa adjacent to the gastric adenocarcinoma, and adenocarcinoma with poorer differentiation had lower TFF1 expression. Conclusions TFF1 expression is increased in gastritis, gastric ulcer and duodenal ulcer, and multiple and compound ulcer has higher TFF1 expression than simple ulcer, suggesting the protective role of TFF1 in gastric mucosa and epithelial restitution. TFF1 may directly contribute to the differentiation of adenocarcinoma, and the poorer the differentiation, the lower the expression of TFF1.
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Relationship between Trefoil Factor 1 expression and gastric mucosa injuries and gastric cancer
World Journal of Gastroenterology, 2005Co-Authors: Ya-pi Lu, Lin WangAbstract:Relationship between Trefoil Factor 1 expression and gastric mucosa injuries and gastric cancer
