Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma

Kim, Su-Mi; Oh, Sun-Ju; Hur, Bang

doi:10.4132/koreanjpathol.2012.46.5.429

Cited by 11 publications

(6 citation statements)

References 30 publications

(56 reference statements)

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“…MUC-4 overexpression is demonstrated in rat cholangiocarcinoma by tissue microarray (Yeh et al, 2009). However, the correlation of MUC-4 expression with aggressive behaviors was not observed in gastric cancer, consistent with other reports (Senapati et al, 2008;Kim et al, 2012), while Tamura et al found that MUC-4 expression was related to lymphatic invasion and lymph node metastasis of gastric cancer (Tamura et al 2012). Another group reported found that the increase in the expression and hypomethylation of MUC-4 gene with the progression of pancreatic ductal adenocarcinoma (Zhu et al, 2011).…”

Section: Discussionsupporting

confidence: 78%

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Xiao¹,

Zhao²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 78%

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Xiao¹,

Zhao²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Recently, EMA mRNA was reported to be up-regulated in a co-culture study of hepatoma cells and activated hepatic stellate cells (HSCs), compared to stromal cells cultured alone [16] . Furthermore, clinical studies have reported a relationship between EMA expression and poor prognosis in various malignant tumors, including lung cancer, gastric cancer, gallbladder cancer, and HCC [17] – [20] . Fibroblast activation protein (FAP), a member of the serine protease family, has been reported to increase stromal cell proliferation and invasiveness, as well as reduce cell apoptosis [21] .…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior

et al. 2014

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Tumor behavior is affected by the tumor microenvironment, composed of cancer-associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (≥5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC.

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“…Some mucins play roles in controlling mineralization, involving bone formation in vertebrates, calcification in echinoderms and nacre formation in mollusks. MUC4 and MUC1, two transmembrane mucins, have been involved in wide-ranging studies in relation to their pathological implication in malignancies and other disease processes due to their overor mis-expression [31,32]. The epithelium separates multicellular animals from the external environment by means of its identity of a transversely connected layer of cells with apical-basal polarity [33].…”

Section: Discussionmentioning

confidence: 99%

Mucin 4 Gene Silencing Reduces Oxidative Stress and Calcium Oxalate Crystal Formation in Renal Tubular Epithelial Cells Through the Extracellular Signal-Regulated Kinase Signaling Pathway in Nephrolithiasis Rat Model

Sun¹,

Zou²,

Wang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Nephrolithiasis plagues a great number of patients all over the world. Increasing evidence shows that the extracellular signal-regulated kinase (ERK) signaling pathway and renal tubular epithelial cell (RTEC) dysfunction and attrition are central to the pathogenesis of kidney diseases. Mucin 4 (MUC4) is reported as an activator of ERK signaling pathway in epithelial cells. In this study, using rat models of calcium oxalate (CaOx) nephrolithiasis, the present study aims to define the roles of MUC4 and ERK signaling pathway as contributors to oxidative stress and CaOx crystal formation in RTEC. Methods: Data sets of nephrolithiasis were searched using GEO database and a heat flow map was drawn. Then MUC4 function was predicted. Wistar rats were prepared for the purpose of model establishment of ethylene glycol and ammonium chloride induced CaOx nephrolithiasis. In order to assess the detailed regulatory mechanism of MUC4 silencing on the ERK signaling pathway and RTEC, we used recombinant plasmid to downregulate MUC4 expression in Wistar rat-based models. Samples from rat urine, serum and kidney tissues were reviewed to identify oxalic acid and calcium contents, BUN, Cr, Ca²⁺ and P³⁺ levels, calcium crystal formation in renal tubules and MUC4 positive expression rate. Finally, RT-qPCR, Western blot analysis, and ELISA were employed to access oxidative stress state and CaOx crystal formation in RTEC. Results: Initially, MUC4 was found to have an influence on the process of nephrolithiasis. MUC4 was upregulated in the CaOx nephrolithiasis model rats. We proved that the silencing of MUC4 triggered the inactivation of ERK signaling pathway. Following the silencing of MUC4 or the inhibition of ERK signaling pathway, the oxalic acid and calcium contents in rat urine, BUN, Cr, Ca²⁺ and P³⁺ levels in rat serum, p-ERK1/2, MCP-1 and OPN expressions in RTEC and H₂O₂ and MDA levels in the cultured supernatant were downregulated, but the GSH-Px, CAT and SOD levels in the cultured supernatant were increased. Moreover, MUC4 silencing or ERK signaling pathway inactivation may decrease the formation of CaOx crystals. Conclusion: Taken together, silencing of MUC4 can inactivate the ERK signaling pathway and further restrain oxidative stress and CaOx crystal formation in RTEC. Thus, MUC4 represents a potential investigative focus target in nephrolithiasis.

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Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma

Cited by 11 publications

References 30 publications

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior

Mucin 4 Gene Silencing Reduces Oxidative Stress and Calcium Oxalate Crystal Formation in Renal Tubular Epithelial Cells Through the Extracellular Signal-Regulated Kinase Signaling Pathway in Nephrolithiasis Rat Model

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