Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice

2004 ◽  
Vol 201 (2) ◽  
pp. 266-276 ◽  
Author(s):  
Luigi Strizzi ◽  
Caterina Bianco ◽  
Nicola Normanno ◽  
Masaharu Seno ◽  
Christian Wechselberger ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transgenic Mice ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related Intestinal Fibrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Jia Wenxiu ◽  
Yang Mingyue ◽  
Han Fei ◽  
Luo Yuxin ◽  
Wu Mengyao ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Intestinal Inflammation ◽  
Epithelial Mesenchymal Transition ◽  
Lymphoid Cells ◽  
Inflammatory Factors ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis

Background and Aims. Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. Methods. Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. Results. High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn’s disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-β1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. Conclusions. TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.

scholarly journals An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

2020 ◽  
Author(s):  
Molly M. Wilson ◽  
Céline Callens ◽  
Matthieu Le Gallo ◽  
Svetlana Mironov ◽  
Qiong Ding ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Molecular Mechanisms ◽  
Mammary Gland Development ◽  
Epithelial Mesenchymal Transition ◽  
Gene Expression Signature ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Tumor Initiating Cells ◽  
Mesenchymal Transition ◽  
Gland Development

AbstractThe Epithelial–Mesenchymal Transition (EMT) and primary ciliogenesis induce stem cell properties in basal Mammary Stem Cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis at intermediate EMT transition states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote BBS11-dependent ubiquitination and inactivation of a central signaling node, GLIS2. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the Mammary-Tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC biology, mammary gland development, and claudin-low breast cancer formation.

scholarly journals Inactivation of RARβ Inhibits Wnt1-induced Mammary Tumorigenesis by Suppressing Epithelial-mesenchymal Transitions

2014 ◽  
Vol 12 (1) ◽  
pp. nrs.12004 ◽  
Author(s):  
Xingxing Liu ◽  
Vincent Giguère
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Mesenchymal Transition ◽  
Integration Site ◽  
Mammary Tumorigenesis ◽  
Tumor Growth Rate ◽  
Cancer Associated Fibroblasts ◽  
Stromal Compartment ◽  
Mesenchymal Transition ◽  
Retinoid Signaling

Retinoic acid receptor β (RARβ) has been proposed to act as a tumor suppressor in breast cancer. In contrast, recent data have shown that RARβ promotes ERBB2-induced mammary gland tumorigenesis through remodeling of the stromal compartment and activation of cancer-associated fibroblasts. However, it is currently unknown whether RARβ oncogenic activity is specific to ERBB2-induced tumors, or whether it influences the initiation and progression of other breast cancer subtypes. Accordingly, we set out to investigate the involvement of RARβ in basal-like breast cancer using mouse mammary tumor virus (MMTV)-wingless-related integration site 1 (Wnt1)-induced mammary gland tumorigenesis as a model system. We found that compared with wild type mice, inactivation of Rarb resulted in a lengthy delay in Wnt1-induced mammary gland tumorigenesis and in a significantly slower tumor growth rate. Ablation of Rarb altered the composition of the stroma, repressed the activation of cancer-associated fibroblasts, and reduced the recruitment of inflammatory cells and angiogenesis. Reduced expression of IGF-1 and activity of its downstream signaling pathway contribute to attenuate EMT in the Rarb-null tumors. Our results show that, in the absence of retinoid signaling via RARβ, reduced IGF-1 signaling results in suppression of epithelial-mesenchymal transition and delays tumorigenesis induced by the Wnt1 oncogene. Accordingly, our work reinforces the concept that antagonizing RARβ-dependent retinoid signaling could provide a therapeutic avenue to treat poor outcome breast cancers.

Hepatitis B virus X protein enhances the development of liver fibrosis and the expression of genes associated with epithelial-mesenchymal transitions and tumor progenitor cells

2019 ◽  
Vol 41 (3) ◽  
pp. 358-367 ◽  
Author(s):  
James Ahodantin ◽  
Bouchra Lekbaby ◽  
Myriam Bou Nader ◽  
Patrick Soussan ◽  
Dina Kremsdorf
Keyword(s):  
Hepatitis B Virus ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Epithelial Mesenchymal Transition ◽  
Biological Effects ◽  
Matrix Remodeling ◽  
X Protein ◽  
Mesenchymal Transition ◽  
B Virus

Abstract The hepatitis B virus X protein (HBx) has pleiotropic biological effects, which underlies its potential role in cell transformation. However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic for the full-length HBx (FL-HBx) were used. To create liver fibrosis, FL-HBx transgenic and control mice were chronically exposed to carbon tetrachloride (CCl4). Modulation of the expression of proteins involved in matrix remodeling, hepatic metabolism and epithelial-mesenchymal transition (EMT) were investigated. In transgenic mice, FL-HBx expression potentiates CCl4-induced liver fibrosis with increased expression of proteins involved in matrix remodeling (Collagen1a, α-Sma, PdgfR-β, MMP-13). In FL-HBx transgenic mice, an increase in EMT was observed with a higher transcription of two inflammatory cytokines (TNF-α and TGF-β) and a decrease of glutamine synthetase expression level. This was associated with a sustained cell cycle and hepatocyte polyploidy alteration consistent with p38 and ERK1/2 overactivation, increase of PLK1 transcription, accumulation of SQSTM1/p62 protein and increase expression of Beclin-1. This correlates with a higher expression of tumor progenitor cell markers (AFP, Ly6D and EpCam), indicating a higher risk of progression from fibrosis to hepatocellular carcinoma (HCC) in the presence of FL-HBx protein. In conclusion, our results show that FL-HBx protein enhances the development of liver fibrosis and contributes to the progression of liver disease from chronic hepatitis to HCC.

scholarly journals Differential effects of Pax3 on expression of polysialyltransferases STX and PST in TGF-β-treated normal murine mammary gland cells

2016 ◽  
Vol 242 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Dong Guo ◽  
Jia Guo ◽  
Xiang Li ◽  
Feng Guan
Keyword(s):  
Cell Adhesion ◽  
Mammary Gland ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Gland Cells ◽  
Neural Cell Adhesion ◽  
Mammary Gland Cells

Glycosylation of certain proteins at the mammalian cell surface is an essential event in carcinogenesis. Sialylation, one type of glycosylation, can act on multiple cell-behaviors, such as migration, growth, and malignant invasion. Two polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST), are responsible for synthesis of polysialic acid on neural cell adhesion molecule. We showed previously that STX and PST are oppositely expressed in normal murine mammary gland cells undergoing transforming growth factor-β-induced epithelial-mesenchymal transition. The molecular basis for regulation of STX and PST remained unclear. In the present study, we observed that transcription factor Pax3 upregulates STX expression, downregulates PST expression, and modulates upregulated expression of PSA, which attaches primarily to neural cell adhesion molecule to form PSA-NCAM. Overexpression of Pax3 in normal murine mammary gland cells transformed the expression of epithelial-mesenchymal transition markers E-cadherin and N-cadherin, and significantly promoted cell migration, but had no effect on cell proliferation.

scholarly journals Expression of Grainyhead-like 2 in the Process of Ductal Development of Mouse Mammary Gland

2021 ◽  
pp. 002215542110137
Author(s):  
Shinya Matsuoka ◽  
Hiroyoshi Suzuki ◽  
Chieko Kato ◽  
Mai Kamikawa-Tokai ◽  
Akihiro Kamikawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Mammary Gland ◽  
Epithelial Mesenchymal Transition ◽  
Combined Treatment ◽  
Myoepithelial Cells ◽  
Mouse Mammary Gland ◽  
Mesenchymal Transition ◽  
Ovariectomized Mice ◽  
Ductal Development

Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial–mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone–dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts:

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