Promoter CpG methylation in cancer cells contributes to the regulation of MUC4

Yamada, Norishige; Nishida, Yukari; Tsutsumida, Hideaki; Goto, Masamichi; Higashi, Michiyo; Nomoto, Mitsuharu; Yonezawa, Suguru

doi:10.1038/sj.bjc.6604845

Cited by 51 publications

(70 citation statements)

References 24 publications

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“…The target region of MSP locates CpG sites 108-112 of MUC4 promoter, which may play an important role in MUC4 expression [23]. Primer sets for amplification of the MUC4 unmethylated and methylated sequences were synthesized as the reference sequence [23]. PCR was performed using a TaKaRa Taq PCR kit (TaKaRa, Otsu, Shiga, Japan).…”

Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

“…Two microgram of DNA per sample was bisulfite converted and cleaned up using an Epitect Bisulfite Kit (Qiagen). The target region of MSP locates CpG sites 108-112 of MUC4 promoter, which may play an important role in MUC4 expression [23]. Primer sets for amplification of the MUC4 unmethylated and methylated sequences were synthesized as the reference sequence [23].…”

Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

“…PCR was performed using a TaKaRa Taq PCR kit (TaKaRa, Otsu, Shiga, Japan). Each MSP reaction incorporated 2 ll of sodium bisulfite-modified DNA, 0.4 lM of each primer, 0.2 mM of each dNTP, 19 PCR buffer, 1.5 mM of MgCl 2 [23], and a water blank was used as a negative control. MSP products were separated electrophoretically on 3% agarose gels and stained with ethidium bromide.…”

Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

“…In addition, recent studies have provided evidence that promoter CpG methylation sites found in pancreatic tumor cells contribute to the regulation of MUC4 gene expression [22,23]. However, no studies have evaluated MUC4 promoter methylation status in tissue specimens.…”

Section: Introductionmentioning

confidence: 96%

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The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma

et al. 2010

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The MUC4 gene could have a key role in the progression of pancreatic cancer, but the quantitative measurement of its expression in clinical tissue samples remains a challenge. The correlations between MUC4 promoter methylation status in vivo and either pancreatic cancer progression or MUC4 mRNA expression need to be demonstrated. We used the techniques of quantitative real-time PCR and DNA methylation-specific PCR combined microdissection to precisely detect MUC4 expression and promoter methylation status in 116 microdissected foci from 57 patients with pancreatic ductal adenocarcinoma. Both mRNA expression and hypomethylation frequency increased from normal to precancerous lesions to pancreatic cancer. Multivariate Cox regression analysis showed that high-level MUC4 expression (P = 0.008) and tumor-node-metastasis staging (P = 0.038) were significant independent risk factors for predicting the prognosis of 57 patients. The MUC4 mRNA expression was not significantly correlated with promoter methylation status in 30 foci of pancreatic ductal adenocarcinoma. These results suggest that high mRNA expression and hypomethylation of the MUC4 gene could be involved in carcinogenesis and in the malignant development of pancreatic ductal adenocarcinoma. The MUC4 mRNA expression may become a new prognostic marker for pancreatic cancer. Microdissection-based quantitative real-time PCR and methylation-specific PCR contribute to the quantitative detection of MUC4 expression in clinical samples and reflect the epigenetic regulatory mechanisms of MUC4 in vivo.

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Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

Section: Dna Extraction From Microdissectates Bisulfite Treatment Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma

et al. 2010

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“…This was also reported that Methylation of CpG near the transcriptional start site was inversely correlated with MUC1 gene expression (Yamada et al, 2008). Similarly, MUC4 expression was also regulated by methylation of CpG sites near the transcriptional start site (N Yamada et al, 2009).…”

Section: 10299 Epigenetic Changes Within Promoter Regions Of Antigenmentioning

confidence: 60%

Epigenetic Changes within the Promoter Regions of Antigen Processing Machinery Family Genes in Kazakh Primary Esophageal Squamous Cell Carcinoma

Sheyhidin

Hasim²,

Zheng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Prognostic value of mucin 4 expression in colorectal adenocarcinomas

Shanmugam

Jhala

Katkoori

et al. 2010

Cancer

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BACKGROUND: Mucin 4 (MUC4) is aberrantly expressed in colorectal adenocarcinomas (CRCs) but its prognostic value is unknown. METHODS: Archival tissue specimens collected from 132 CRC patients who underwent surgical resection without presurgery or postsurgery therapy were evaluated for expression of MUC4 by using a mouse monoclonal antibody and horseradish peroxidase. MUC4 expression levels were correlated with clinicopathologic features and patient survival. Survival was estimated by both univariate Kaplan-Meier and multivariate Cox regression methods. RESULTS: In both normal colonic epithelium and CRCs, MUC4 staining was localized primarily in the cytoplasm. The optimal immunostaining cutoff value (!75% positive cells and an immunostaining score !2.0), which was derived by using the bootstrap method, was used to categorize CRCs into groups of high expression (33 of 132 patients; 25%) or low expression (99 of 132 patients; 75%). Patients who had early stage tumors (stages I and II) with high MUC4 expression had a shorter disease-specific survival (log-rank; P ¼ .007) than patients who had with low expression. Patients who had advanced-stage CRCs (stages III and IV) did not demonstrate such a difference (logrank; P ¼ .108). Multivariate regression models that were generated separately for patients with early stage and advanced-stage CRC confirmed that increased expression of MUC4 was an independent indicator of a poor prognosis only for patients who had early stage CRCs (hazard ratio, 3.77; 95% confidence interval, 1.46-9.73). CONCLU-SIONS: The current results indicated that increased MUC4 expression is a predictor of poor survival in CRC, specifically for patients who have early stage tumors. Cancer 2010;116;3577-86.

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Promoter CpG methylation in cancer cells contributes to the regulation of MUC4

Cited by 51 publications

References 24 publications

The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma

The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma

Epigenetic Changes within the Promoter Regions of Antigen Processing Machinery Family Genes in Kazakh Primary Esophageal Squamous Cell Carcinoma

Prognostic value of mucin 4 expression in colorectal adenocarcinomas

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