Trefoil factors

Regalo, Gonçalo; Wright, Nicholas; Machado, José Carlos

doi:10.1007/s00018-005-5478-4

Cited by 53 publications

(12 citation statements)

References 84 publications

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“…Of interest was the dramatic up-regulation of another ER-regulated gene, TFF1 [33], trefoil factor 1 (Fig. 2C), which is normally expressed in the epithelium of the breast and ovary [34], [35]. It is also expressed in gastric mucosal cells, where its function is to stabilize the mucosal layer and protect tissue from cellular injury [36].…”

Section: Resultsmentioning

confidence: 99%

Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma

et al. 2013

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While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERα expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERα overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERα overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression of tumor growth, in vitro and potentiation of single agent activity in vivo in nude mice bearing xenografts. Thus, we demonstrate that exploiting adaptive feedback after MEKi can be used to sensitize ERα-positive tumors to hormonal therapy, and propose that this strategy may have broader clinical utility in ERα-positive ovarian carcinoma.

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Section: Resultsmentioning

confidence: 99%

Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma

et al. 2013

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“…Thus, TFF1 messenger RNA and/or protein have been shown to be focally expressed by normal mammary ducts (Poulsom et al , 1997; Wilson et al , 2006; Madsen et al , 2007; Vestergaard et al , 2008), and TFF1 is a human milk component (Vestergaard et al , 2008). However, in breast cancers, as in various other cancers, TFF1 expression is not downregulated as observed in gastric tumors, but strongly induced (Ribieras et al , 1998; Regalo et al , 2005), suggesting a possible function as an oncogene (Perry et al , 2008). …”

Section: Discussionmentioning

confidence: 87%

“…Indeed, TFF1 promotes epithelial restitution after injury and protects the integrity of the epithelial barrier (Hoffmann, 2005). Moreover, TFF1 is also expressed, but to a lesser extent, by normal epithelial cells of numerous organs (eyes, lung, ovary and salivary gland) (Regalo et al , 2005; Madsen et al , 2007; Buron et al , 2008). To date, the TFF1 function during malignant processes is not clearly defined, as epithelial cell transformation might lead to downregulation of TFF1 expression (that is, in the stomach) or to the induction of TFF1 expression (that is, in various organs).…”

Section: Introductionmentioning

confidence: 99%

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

et al. 2011

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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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“…However, the higher levels of TFF3 levels in the serum of lung cancer patients may also be attributed to the histological changes in other tissues, especially for patients with late stages of lung cancers, since TFF1 is mainly expressed in the stomach and colon; TFF2 is mainly localized in the stomach; TFF3 is principally expressed in the intestines (22,53). We analyzed the correlation between the levels of serum TFF3 and the stages of the investigated 130 lung cancer patients using the statistical software.…”

Section: Discussionmentioning

confidence: 99%

“…Although TFFs have been involved in the protection of the gastrointestinal tract against mucosal damage (11), their oncogenic potential has been extensively reported, including their roles in cell proliferation (12–15), apoptosis (12–14,16,17), migration and invasion (14,16,18,19) and angiogenesis (20,21). TFF proteins levels have been found to be related to the development of breast cancer (22–33), gastric cancer (21,22,34–38), colon cancer (39,40), and prostate cancer (41–43). It has also been reported that TFF proteins are related to lung cancers (23,44–48).…”

Section: Introductionmentioning

confidence: 99%

Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer

Yang²,

Ma³

et al. 2011

Oncology Reports

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Lung cancer is the most common cause of cancer-related deaths in the world. The trefoil factor (TFF) family is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3. TFF protein levels have been found to be related to the development of various types of cancer. However, it is still unclear whether TFF proteins are differentially expressed in the serum of different histological subtypes of lung cancer compared to healthy individuals. In this study, we investigated the levels of TFF proteins in serum and lung tissues of 130 lung cancer patients (58 squamous cell lung carcinoma cases, 43 adenocarcinoma cases and 29 SCLC cases) and 60 healthy individuals. It was found that TFF1 and TFF2 have similar or slightly higher levels in these three subtypes of lung cancer compared to healthy individuals, while TFF3 levels were significantly higher in the examined lung cancer cases compared to healthy individuals. Immunoblot analyses of TFF1, TFF2 and TFF3 indicated that lung cancer tissues and lung cancer cell lines have a higher expression of the TFF3 protein, but not of TFF1 or TFF2 proteins, compared to tissues from healthy individuals or from the normal cell line. Quantitative RT-PCR analysis indicated higher levels of TFF3, but not TFF1 and TFF2, transcripts in lung cancer tissues or cell lines. These results show increased TFF3 levels in serum and lung tissues, suggesting that TFF3 may serve as a promising, easily detected biomarker of lung cancer.

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Trefoil factors

Cited by 53 publications

References 84 publications

Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma

Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer

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