The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor– and MAP kinase–dependent interregulation

Taupin, Douglas; Wu, Deng Chyang; Jeon, Woo Kyu; Devaney, Kathryn; Wang, Yichen; Podolsky, Daniel K.

doi:10.1172/jci3304

Cited by 140 publications

(116 citation statements)

References 52 publications

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“…The results of several recent studies seem to support the idea that epidermal growth factor receptors, mitogen-activated protein kinase, and adenomatous polyposis coli (APC)/E-cadherin/␤-catenins are regulated by the trefoil peptides (Efstathiou et al, 1999;Liu et al, 1997;Taupin et al, 1999). It was reported that E-cadherin expression was reduced in the restitutive monolayer epithelium of ulcers in which trefoil peptides were expressed (Hanby et al, 1996).…”

Section: Discussionmentioning

confidence: 91%

Expression of Cytoplasmic TFF2 Is a Marker of Tumor Metastasis and Negative Prognostic Factor in Gastric Cancer

Dhar

Wang

Maruyama

et al. 2003

Laboratory Investigation

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SUMMARY:Trefoil factor family 2 (TFF2) is a small peptide constitutively expressed in the gastric mucosa, where it plays a protective role in restitution of gastric mucosa. TFF2 has also been shown to be expressed in some gastric cancers, but its role in tumor metastasis and patient prognosis has not been examined. In this study, we examined TFF2 expression at both the mRNA and protein levels and correlated these results with the clinicopathologic characteristics and prognosis of gastric cancer patients. Among the 144 curatively resected samples, 43 (30%) were positive for TFF2. TFF2 expression was preferentially observed in the infiltrating tumor cells sparing the superficial cells. Significantly increased expression of TFF2 was noted in large tumors of the diffuse type. An increased prevalence of TFF2 expression was also found in tumors with advanced T and N stage and in patients with lymphatic and venous invasion. Accordingly, patients with TFF2-expressing tumors had a significantly worse disease-free survival, and in multivariate analysis, this finding remained significant as an independent prognostic factor. Taken together, our results suggest that TFF2 expression may play a role in gastric cancer invasion and as such could be a useful target for therapeutic intervention. (Lab Invest 2003, 83:1343-1352.

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Section: Discussionmentioning

confidence: 91%

Expression of Cytoplasmic TFF2 Is a Marker of Tumor Metastasis and Negative Prognostic Factor in Gastric Cancer

Dhar

Wang

Maruyama

et al. 2003

Laboratory Investigation

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“…A time course study revealed that the TFF2 induction occurred within 6 h of IFNg treatment. This was not surprising since TFF2 has been reported to be an immediate-early gene, in response to EGF-or autoinduction, 24,25 but has not been shown to be regulated by proinflammatory cytokines. Expression of the pepsinogen II (PGC), pepsinogen I (PGA), intrinsic factor and H þ , K þ -ATPase genes was also detected in this gastric cancer cell line by RT-PCR (Figure 8a).…”

Section: Ifnc Induces the Expression Of Muc6 And Tff2 And Hypertrophymentioning

confidence: 97%

Interferon gamma induction of gastric mucous neck cell hypertrophy

Kang

Rathinavelu

Samuelson

et al. 2005

Laboratory Investigation

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Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (GÀ/À) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not GÀ/À stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the GÀ/À model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNc) was the most abundant proinflammatory cytokine in the GÀ/À stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both GÀ/À and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNc induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNc, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.

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“…Ulcer healing is a complex process, which involves cell migration, proliferation, re-epithelialization, angiogenesis, and matrix deposition, all ultimately leading to scar formation (1-9) ( Figure 2). All these processes are controlled by growth factors, transcription factors and cytokines (2,3,(9)(10)(11).…”

Section: Plcγmentioning

confidence: 99%

“…In addition, the epithelial cells from the base of the ulcer margin form tubes composed of ulcer-associated cell lineage, which invade granulation tissue, migrate toward the surface, branch and undergo transformation into gastric glands within the ulcer scar (3,7,13) (Figure 2). The major stimuli for cell proliferation, division, migration and re-epithelialization are growth factors (1,3,(9)(10)(11). In addition to the initial pool of growth factors derived from the platelets, macrophages and injured tissue, ulceration triggers in cells lining mucosa of the ulcer margin, genes encoding for the growth factors (e.g., EGF, bFGF, HGF, VEGF and trefoil peptides) and Cox2 in a wellsynchronized spatial and temporal manner (3,11,14).…”

Section: Cellular and Molecular Events In The Ulcer Margin (Figure 3)mentioning

confidence: 99%

“…Re-epithelialization, the migration of epithelial cells from the ulcer margin to restore epithelial continuity, is an essential process for cutaneous and gastrointestinal wound/ulcer healing- Figure 2 (1,3,7,9,10). This process is essential because a continuous epithelial "barrier" protects granulation tissue from mechanical and chemical injury or infection.…”

Section: Cellular and Molecular Events In The Ulcer Margin (Figure 3)mentioning

confidence: 99%

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Cellular and Molecular Mechanisms of Gastrointestinal Ulcer Healing

2005

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The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor– and MAP kinase–dependent interregulation

Cited by 140 publications

References 52 publications

Expression of Cytoplasmic TFF2 Is a Marker of Tumor Metastasis and Negative Prognostic Factor in Gastric Cancer

Expression of Cytoplasmic TFF2 Is a Marker of Tumor Metastasis and Negative Prognostic Factor in Gastric Cancer

Interferon gamma induction of gastric mucous neck cell hypertrophy

Cellular and Molecular Mechanisms of Gastrointestinal Ulcer Healing

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