Establishment and characterisation of six human biliary tract cancer cell lines

Jl, Ku; Ka, Yoon; Ij, Kim; Wh, Kim; Jang, Jin–Young; Ks, Suh; Sw, Kim; Yh, Park; Hwang, JH; Yb, Yoon; Park, JG

doi:10.1038/sj.bjc.6600440

Cited by 76 publications

(61 citation statements)

References 23 publications

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“…INK4a , hMLH1, CDX1, RASSF1A, and Ecadherin genes, is involved in colorectal carcinogenesis (reviewed by Trojan et al, 2000;Esteller et al, 2001;Ku et al, 2002;Suh et al, 2002;van Engeland et al, 2002). In this study, we analysed the methylation status of the promoter region and performed mutational analysis on the RUNX3 gene in 32 colorectal cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal de novo methylation of CpG islands occurs frequently in human cancers including colorectal cancers; moreover, hypermethylation of CpG islands is known to be associated with transcriptional inactivation (Melki et al, 2000;Trojan et al, 2000;Esteller et al, 2001;Song et al, 2001;Zo¨chbauer-Mu¨ller et al, 2001;Ku et al, 2002;Suh et al, 2002;van Engeland et al, 2002;Yang et al, 2002). It has also been reported that transcriptional inactivation by hypermethylation of the promoter region in some genes, for example, APC, LKB1, p16…”

Section: Discussionmentioning

confidence: 99%

“…Such inactivation is observed in various human cancers, in genes including RB, p16, VHL, BRCA1, E-cadherin, APC, hMLH1, FHIT, COX2, and CDX1 (reviewed by Melki et al, 2000;Song et al, 2001;Zo¨chbauer-Mu¨ller et al, 2001;Ku et al, 2002;Suh et al, 2002;Yang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines

Kang

Shin

et al. 2004

Oncogene

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It was recently reported that RUNX3 gene expression is significantly downregulated in human gastric cancer cells due to hypermethylation of its promoter region or hemizygous deletion (Cell, 109, 2002). To verify the genetic alterations and methylation status of the RUNX3 gene in colorectal carcinogenesis, we analysed for mutations, loss of heterozygosity (LOH), and RUNX3 gene promoter hypermethylation, in 32 colorectal cancer cell lines. RT-PCR analysis showed undetectable or low RUNX3 expression in 16 cell lines, and no mutations were found in the RUNX3 gene by PCR-SSCP analysis. Of these 16 cell lines, hypermethylation of the RUNX3 promoter was confirmed in 12. The following observations were made: (i) RUNX3 was re-expressed after 5-aza-2 0 -deoxycytidine treatment, (ii) the RUNX3 promoter was found to be methylated by MS-PCR, and (iii) hypermethylation of the RUNX3 promoter was confirmed by direct sequencing analysis after sodium bisulfite modification in the above 12 cell lines. RUNX3 was neither methylated nor expressed in four cell lines. Of these four, microsatellite instability (MSI) at the RUNX3 locus was found in three, SNU-61 (D1S246), SNU-769A, and SNU-769B (D1S199). This study suggests that transcriptional repression of RUNX3 is caused by promoter hypermethylation of the RUNX3 CpG island in colorectal cancer cell lines, and the results of these experiments may contribute to an understanding of the role of RUNX3 inactivation in the pathogenesis of colorectal cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines

Kang

Shin

et al. 2004

Oncogene

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“…Previous investigators have evaluated homozygous deletion of the p16 gene in a small series of biliary tract and gallbladder cancer cell lines. Ku et al [25] have reported that homozygous deletion of the p16 gene was detected in three of six (50%) gallbladder cell lines. Yoshida et al [9] have reported that homozygous deletion of the p16 gene was detected in one of two gallbladder cell lines and in two biliary tract cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown a frequency of p16 mutation of 0%-80% in gallbladder and biliary tract cancer and cell lines [9,12,14,25] . Ueki et al have reported that 13 of 53 (24.5%) cases of gallbladder cancer showed non-silent p16 gene mutations.…”

Section: Discussionmentioning

confidence: 99%

Two distinct pathways of p16 gene inactivation in gallbladder cancer

Hiroyuki¹

2007

WJG

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AIM:To examine the mechanism of inactivation of the p16 gene in gallbladder cancer, and to investigate p16 alterations and their correlation with clinicopathological features. METHODS:Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression, loss of heterozygosity (LOH), homozygous deletion and promoter hypermethylation using immunohistochemistry, microsatellite analysis, quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR, respectively. In addition, mutations were examined by direct DNA sequencing. RESULTS:Homozygous deletions of the p16 gene exon2, LOH at 9p21-22, p16 promoter hypermethylation, and loss of p16 protein expression were detected in 26.0% (13/50), 56.9% (29/51), 72.5% (37/51) and 62.7% (32/51), respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene, a combination LOH and promoter hypermethylation, and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene, respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION:Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion, a combination of LOH and promoter hypermethylation, and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.

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K‐ras, p53 mutations, and microsatellite instability (MSI) in gallbladder cancer

Saetta

2006

Journal of Surgical Oncology

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Despite the considerable progress in understanding the molecular pathology of carcinogenesis, the genetic mechanisms underlying the development and progression of gallbladder cancer (GC) are poorly understood. The survival of GC patients is generally poor. Therefore, it is very useful to define valuable prognostic factors. The most extensively studied oncogenes in gallbladder carcinogenesis are ras, commonly mutated in neoplasms of the gastrointestinal tract. K-ras oncogene is altered in a subset of gallbladder patients and mainly in those having anomalous junction of the pancreaticobiliary tract. Most of the studies of genetic abnormalities in GC have focused on p53 gene. p53 mutation/overexpression and/or LOH is present in more than 50% of gallbladder carcinomas, suggesting an important role in their pathogenesis. However, these results have not any predictive value yet. Moreover, the involvement of an alternative molecular pathway, that of microsatellite instability (MSI), is found in a limited group of GC patients. Additional research is necessary to establish its possible relation to defects of the mismatch repair (MMR) system and its proposed prognostic significance. Further elucidation of the molecular events specific to GC will help to identify novel molecular targets for the diagnosis and clinical management of the patients.

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Establishment and characterisation of six human biliary tract cancer cell lines

Cited by 76 publications

References 23 publications

Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines

Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines

Two distinct pathways of p16 gene inactivation in gallbladder cancer

K‐ras, p53 mutations, and microsatellite instability (MSI) in gallbladder cancer

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