• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.89-94
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• 2018

Purpose: To investigate the relationship between MUC expression and clinicopathologic factors in advanced gastric cancer. Methods: A total of 237 tumor specimens were assessed for MUC expression by immunohistochemistry. The clinicopathologic factors were investigated with MUC1, MUC2, MUC5AC, and MUC6. Results: MUC1, MUC2, MUC5AC, and MUC6 expression was identified in 148 of 237 (62.4%), 141 of 237 (59.5%), 186 of 237 (78.5%), and 146 of 237 (61.6%) specimens, respectively. MUC1 expression was correlated with age, human epidermal growth factor receptor 2 (HER2) status, lymphatic invasion, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC1expression and lymphatic invasion, diffuse type of Lauren classification. MUC5AC expression was correlated with HER2 status, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC5AC expression and HER2 status, diffuse and mixed type of Lauren classification. MUC2 and MUC6 expression were not correlated with clinicopathologic factors. The patients of MUC1 expression had poorer survival than those without MUC1 expression, but MUC2, MUC5AC or MUC6 were not related to survival. In an additional multivariate analysis that used the Cox proportional hazards model, MUC1 expression was not significantly correlated with patient survival independent of age, N-stage, and venous invasion. Conclusion: When each of these four MUCs expression is evaluated, in light of clinicopathologic factors, MUC1 expression may be considered as a prognostic factor in patients with advanced gastric cancer. Therefore, careful follow-up may be necessary because the prognosis is poor when MUC1 expression is present.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.198-198
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• 1998

Muc1 mucin is found in a variety of epithelial tissue and is overexpressed in several epithelial cancer. Recently it is alsol reported that primary Hamster tracheal surface epithelial(HTSE) cells express Muc1 protein and cDNA encoding HTSE muc1 protein has been cloned. Although numerous monoclonal antibodies (mAbs) to human muncins, particularly Muc1 have been produced, no such antibodies to murine Muc1 have been described. We now describe monoclonal antibody, called mAb M1CT, produced to C-terminal region of HTSE Muc1 protein by immunising mice with a glutathion-s-transferase linked fusion protein. In this study, using this antibody(mAb M1CT) we investigated the effect of RA on the expression of Muc1 in HTSE cells. Retinoic acid(RA) plays an essential role in maintaining normal differentiation of tracheal epithelial cells. With RA-deficiency tracheocytes undergo squamous metaplasia, an abnormal differentiation that can be reversed by RA. We had primary culture of HTSE cells under different concentrations of RA. Culture was maintained until the direction of differentiation was determined. Then Western blot analysis with mAb M1CT was performed with the cell lysates from the culture. The expression of Muc1 protein was decreased in dose-dependent manner as the concentration of retinoic acid was decreased. Our result indicates that the expression of Muc1 protein is coordinately regulated with airway mucous cell differentiation by RA pathway. And the antibody, mAb M1CT, produced in this study should provide useful tool to study the expression of Muc1 mucin in differentiation process or disease.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.127-131
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• 2013

Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.60-68
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• 2017

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-${\alpha}$ in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone ($1{\mu}g/mL$) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-${\alpha}$ in culture supernatants were measured using enzyme-linked immunosorbent assay. Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-${\alpha}$. Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-${\alpha}$ production in PMA-induced human airway epithelial cells.

• Molecules and Cells
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• v.46 no.11
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• pp.700-709
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• 2023

Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCβ3-Ca²⁺ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.

• BMB Reports
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• v.50 no.10
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• pp.516-521
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• 2017

$CLB_{2.0}$, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates $CLB_{2.0}$-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by $CLB_{2.0}$. While the overexpression of claudin-1 decreased $CLB_{2.0}$-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. $CLB_{2.0}$-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetyl-cysteine inhibited $CLB_{2.0}$-induced IL-6 secretion, thereby decreasing the $CLB_{2.0}$-induced MUC5AC expression, whereas $CLB_{2.0}$-induced MUC1 expression increased. $CLB_{2.0}$ activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased $CLB_{2.0}$-induced MUC5AC expression. These findings suggest that $CLB_{2.0}$-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates $CLB_{2.0}$-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.21-30
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• 2003

Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

• BMB Reports
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• v.54 no.8
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• pp.425-430
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• 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6349-6355
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• 2012

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.