Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions

Klump, Bodo; Hsieh, Chih-Jen; Nehls, Oliver; Dette, S.; Holzmann, Karlheinz; Kießlich, Ralf; Jung, Michael; Sinn, U.; Ortner, Maria-Anna; Porschen, Rainer; Gregor, Michael

doi:10.1038/sj.bjc.6600734

Cited by 46 publications

(35 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…INK4A due either to gene mutations or epigenetic silencing by DNA methylation (41)(42)(43). Although we saw modest effects of U0126 on cyclin D1 expression in two of eight cell lines, the most consistent change that we observed in eight of eight pancreatic cancer cell lines tested was elevated p27…”

Section: Resultsmentioning

confidence: 62%

Pharmacologic Inhibition of RAF→MEK→ERK Signaling Elicits Pancreatic Cancer Cell Cycle Arrest Through Induced Expression of p27Kip1

et al. 2005

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 62%

Pharmacologic Inhibition of RAF→MEK→ERK Signaling Elicits Pancreatic Cancer Cell Cycle Arrest Through Induced Expression of p27Kip1

et al. 2005

View full text Add to dashboard Cite

show abstract

“…On the other hand, because of frequent hypermethylation of the CDH13 gene and the high sensitivity of MSP, which can detect 1 methylated allele among 1000 unmethylated alleles, 27) it can potentially be used for early detection and monitoring of pancreatic cancer by the detection of the CDH13 methylation status in clinical samples such as serum, stool, pancreatic juice, and duodenal fluid. 18,28,29) We thank Y. Nishikawa and M. Taguchi for their technical assistance. 2) Well-mod, well or moderately differentiated adenocarcinoma; poor, poorly differentiated adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer

et al. 2004

View full text Add to dashboard Cite

It has recently been reported that CDH13 expression is silenced by aberrant methylation of the promoter region in several cancers. We examined the methylation status of the CDH13 gene in pancreatic cancer using methylation-specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6 pancreatic cancer cell lines examined. To confirm the status of the CDH13 gene in relation to the methylation pattern, we next examined CDH13 expression in these cell lines using reverse transcription (RT)-PCR. As expected, no CDH13 expression was detected in any of the 6 pancreatic cancer cell lines. Moreover, 5-aza-2′ ′ ′ ′-deoxycytidine (5-azadC) treatment of CDH13-methylated cell lines led to restoration of CDH13 expression. ancreatic cancer is one of the most aggressive cancers, and is the fifth leading cause of cancer mortality in the Western population.1) The prognosis is poor, and 5-year survival is rare. 2)Pancreatic carcinogenesis is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells.3) Mutations in proto-oncogenes such as K-ras and tumor suppressor genes such as p16, p53, and DPC4 are well known. [4][5][6][7] The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and normal growth. However, further studies of the genetic alterations are needed to clarify fully the biological character of pancreatic cancer.In recent years, there has been increasing interest in a large family of transmembrane glycoproteins, the cadherins. Cadherins are prime mediators of calcium-dependent cell-cell adhesion in normal cells and are also involved in contact inhibition of cell growth by inducing cell cycle arrest. 8, 9) Loss of their expression has been described in many epithelial cancers and may play a role in tumor cell invasion and metastasis. 10,11) Recently, aberrant methylation of the CDH13 (H-cadherin) gene associated with gene silencing has been reported in several primary tumors including breast, lung, colorectal, and ovarian cancers, and myeloid leukemia.12-16) These reports suggested that CDH13 may be an important gene for the progression of cancer and prompted us to examine CDH13 status in pancreatic cancer.In this study, we first examined the methylation status and gene expression of CDH13 in pancreatic cancer cell lines using methylation-specific PCR (MSP) and reverse transcription-PCR (RT-PCR), respectively. We then examined the methylation status of the CDH13 gene in primary pancreatic cancers and corresponding normal pancreatic tissues derived from 33 patients, and evaluated the correlation between the methylation status and the clinicopathological findings. Materials and MethodsSample collection and DNA preparation. Six pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2, MIA PaCa-2, and SW1990) and 1 colorectal cancer cell line (SW480) were obtained from American Type Culture Collection (Manassas, VA). They were grown in RPMI 1640 supplemented with 10% fetal bovine serum and incubated in 5% CO 2 at 37°C....

show abstract

“…In addition, other mutations, such as those of the p16, DPC4, and BRCA2 genes or promoter methylation of tumor suppressor, which evidently play role in a linear tumor progression model of pancreatic carcinoma, also should be looked for in lesions that might be responsible for the presumed pancreatic carcinoma sequence in chronic pancreatitis [25][26][27][28][29][30] .…”

Section: Discussionmentioning

confidence: 99%

Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

Ren¹,

Xu²,

Li³

et al. 2004

WJG

View full text Add to dashboard Cite

AIM:To investigate frequency and clinical significance of Kras mutations in pancreatic diseases and to identify its diagnostic values in pancreatic carcinoma. METHODS:117 ductal lesions were identified in the available sections from pancreatic resection specimens of pancreatic ductal adenocarcinoma, comprising 24 pancreatic ductal adenocarcinoma, 19 peritumoral ductal atypical hyperplasia, 58 peritumoral ductal hyperplasia and 19 normal duct at the tumor free resection margin. 24 ductal lesions were got from 24 chronic pancreatitis. DNA was extracted. Codon 12 K-ras mutations were examined using the twostep polymerase chain reaction (PCR) combined with restriction enzyme digestion, followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis and by means of automated DNA sequencing.RESULTS: K-ras mutation rate of the pancreatic carcinoma was 79%(19/24) which was significantly higher than that in the chronic pancreatitis 33%(8/24) (P<0.01). It was also found that K-ras mutation rate was progressively increased from normal duct at the tumor free resection margin, peritumoral ductal hyperplasia, peritumoral ductal atypical hyperplasia to pancreatic ductal adenocarcinoma. The mutation pattern of Kras 12 codon of chronic pancreatitis was GGT GAT, GGT and CGT, which is identical to that in pancreatic carcinoma.CONCLUSION: K-ras mutation may play a role in the malignant transformation of pancreatic ductal cell. K-ras mutation was not specific enough to diagnose pancreatic carcinoma.Ren YX, Xu GM, Li ZS, Song YG. Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases. World J Gastroenterol 2004; 10(6): 881-884

show abstract

Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions

Cited by 46 publications

References 32 publications

Pharmacologic Inhibition of RAF→MEK→ERK Signaling Elicits Pancreatic Cancer Cell Cycle Arrest Through Induced Expression of p27Kip1

Pharmacologic Inhibition of RAF→MEK→ERK Signaling Elicits Pancreatic Cancer Cell Cycle Arrest Through Induced Expression of p27Kip1

Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer

Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

Contact Info

Product

Resources

About