18 research outputs found
Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice
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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Race-based Outcomes of Thoracic Aortic Aneurysms and Dissections in the Global Registry for Endovascular Aortic Treatment
This study characterizes racial differences in presentation, as well as short- and long-term outcomes following endovascular treatment of thoracic aortic aneurysm (TAA) and type B aortic dissection (TBAD).We queried the Gore Global Registry for Endovascular Aortic Treatment (GREAT) for thoracic endovascular aortic repairs (TEVARs) performed between 2010-2016 and followed through 2022. Pathologies represented were descending TAA, complicated TBAD, and uncomplicated TBAD. Using standard statistical tests, we compared overall and pathology-specific demographics, procedural factors, and outcomes among Black and White patients undergoing TEVAR.We identified 438 TEVAR cases, including 236 descending TAA, 121 complicated TBAD, and 74 uncomplicated TBAD. Overall, Black patients were younger and had higher incidence of renal insufficiency (P=.001), whereas White patients had more chronic obstructive pulmonary disease (P=.003) and cardiac arrhythmias (P=.037). In patients treated for descending TAA, Black patients had increased device/procedure-related complications (34.3% vs 17.4%, P=.014), conversion to open repair (2.9% vs 0%, P=.011) and type II endoleak (5.7% vs 1.0%, P=.040) but no differences in mortality, length of hospital stay, or major adverse cardiovascular events. Whereas outcomes of TEVAR for uncomplicated TBAD were comparable, Black patients more frequently presented with complicated TBAD than White patients (Black: 40.5% vs White: 24.8%, P=.008) and had subsequently greater reintervention rate (28.1% vs 12.4%, P=.012), all-cause mortality (HR 4.28, 95% CI 1.74-10.5, P=.002) and aortic-related mortality (HR 16.7, 95% CI 1.49-186, P=.022).Despite increased device- and procedure-related complications, similar short and long-term outcomes are achieved in Black and White patients undergoing TEVAR for descending TAA and uncomplicated TBAD. However, Black patients are more likely to present with, require reintervention, and suffer mortality from complicated TBAD.•Type of Research: Retrospective analysis of thoracic endovascular aortic repair (TEVAR) cases in the Gore Global Registry for Endovascular Aortic Treatment.•Key Findings: In 438 TEVAR cases for descending thoracic aortic aneurysm and dissection, Black patients presented with more complicated type B aortic dissections (B: 40.5% vs W: 24.8%). They also required more reinterventions (B: 28.1% vs W: 12.4%) and had greater all-cause (B: 37.5% vs W: 23.6%) and aortic-related (B: 9.4% vs W: 1.1%) mortality than White patients.•Take Home Message: Whereas outcomes of TEVAR for descending thoracic aortic aneurysms and uncomplicated type B aortic dissection are comparable, Black patients with complicated type B aortic dissection have greater need for reintervention and higher mortality
Cytosolic Levels of An Estrogen-Induced Breast Cancer-Associated Peptide (TFF1/pS2) in Colorectal Cancer: Clinical Significance and Relationship with Steroid Receptors
Functional Genomics of the Endocrine Pancreas: The Pancreas Clone Set and PancChip, New Resources for Diabetes Research
The trefoil factor interacting protein TFIZ1 binds the trefoil protein TFF1 preferentially in normal gastric mucosal cells but the co-expression of these proteins is deregulated in gastric cancer
The gastric tumour suppressor trefoil protein TFF1 is present as a covalently bound heterodimer with a previously uncharacterised protein, TFIZ1, in normal human gastric mucosa. The purpose of this research was firstly to examine the molecular forms of TFIZ1 present, secondly to determine if TFIZ1 binds other proteins apart form TFF1 in vivo, thirdly to investigate if TFIZ1 and TFF1 are co-regulated in normal gastric mucosa and fourthly to determine if their co-regulation is maintained or disrupted in gastric cancer. We demonstrate that almost all human TFIZ1 is present as a heterodimer with TFF1 and that TFIZ1 is not bound to either of the other two trefoil proteins, TFF2 and TFF3. TFIZ1 and TFF1 are co-expressed by the surface mucus secretory cells throughout the stomach and the molecular forms of each protein are affected by the relative abundance of the other. TFIZ1 expression is lost consistently, early and permanently in gastric tumour cells. In contrast, TFF1 is sometimes expressed in the absence of TFIZ1 in gastric cancer cells and this expression is associated with metastasis (lymph node involvement: p = 0.007). In conclusion, formation of the heterodimer between TFIZ1 and TFF1 is a specific interaction that occurs uniquely in the mucus secretory cells of the stomach, co-expression of the two proteins is disrupted in gastric cancer and expression of TFF1 in the absence of TFIZ1 is associated with a more invasive and metastatic phenotype. This indicates that TFF1 expression in the absence of TFIZ1 expression has potentially deleterious consequences in gastric cancer